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Meng Y, Zhang J, Liu Y, Zhu Y, Lv H, Xia F, Guo Q, Shi Q, Qiu C, Wang J. The biomedical application of inorganic metal nanoparticles in aging and aging-associated diseases. J Adv Res 2025; 71:551-570. [PMID: 38821357 DOI: 10.1016/j.jare.2024.05.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 05/10/2024] [Accepted: 05/22/2024] [Indexed: 06/02/2024] Open
Abstract
Aging and aging-associated diseases (AAD), including neurodegenerative disease, cancer, cardiovascular diseases, and diabetes, are inevitable process. With the gradual improvement of life style, life expectancy is gradually extended. However, the extended lifespan has not reduced the incidence of disease, and most elderly people are in ill-health state in their later years. Hence, understanding aging and AAD are significant for reducing the burden of the elderly. Inorganic metal nanoparticles (IMNPs) predominantly include gold, silver, iron, zinc, titanium, thallium, platinum, cerium, copper NPs, which has been widely used to prevent and treat aging and AAD due to their superior properties (essential metal ions for human body, easily synthesis and modification, magnetism). Therefore, a systematic review of common morphological alternations of senescent cells, altered genes and signal pathways in aging and AAD, and biomedical applications of IMNPs in aging and AAD is crucial for the further research and development of IMNPs in aging and AAD. This review focus on the existing research on cellular senescence, aging and AAD, as well as the applications of IMNPs in aging and AAD in the past decade. This review aims to provide cutting-edge knowledge involved with aging and AAD, the application of IMNPs in aging and AAD to promote the biomedical application of IMNPs in aging and AAD.
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Affiliation(s)
- Yuqing Meng
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Junzhe Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yanqing Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yongping Zhu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Haining Lv
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Fei Xia
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Qiuyan Guo
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Qianli Shi
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Chong Qiu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Jigang Wang
- Department of Urology, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China.
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Cao Y, Wang Y, Xia D. Investigating the Associations Between Hmga2 Overexpression, R-Loop Reduction, and Bone Loss in Aging Mice. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:820. [PMID: 40428778 PMCID: PMC12113323 DOI: 10.3390/medicina61050820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/20/2025] [Accepted: 04/25/2025] [Indexed: 05/29/2025]
Abstract
Background and Objectives: Aging-related bone loss still lacks interventions. As bone marrow-derived mesenchymal stem cells (BMSCs) undergo aging, R-loop-induced DNA replication stress impairs the osteogenic ability of BMSCs. High-mobility group A-2 (Hmga2) acts as a DNA-binding protein, and the understanding of its underlying mechanisms is crucial for developing effective preventive and therapeutic strategies. Materials and Methods: Aging mice were used as the experimental model, and mouse BMSCs were isolated from their femurs. Hmga2 was achieved through specific gene delivery methods. R-loop formation was detected using dot blotting, chromatin immunoprecipitation (ChIP), and DNA-RNA immunoprecipitation (DRIP) assays. Osteogenic differentiation was evaluated. Results: R-loops were highly accumulated in aging BMSCs. Notably, the key regulator Hmga2 reversed the accumulation of R-loops in aging BMSCs. Hmga2 overexpression significantly decreased the senescence and improved the osteogenic differentiation of aging mBMSCs. Mechanistically, R-loop-forming sequence (RLFS) regions were confirmed in key osteogenesis-related genes, including runt-related transcription factor 2 (Runx2). Hmga2 bound to the RLFS region of Runx2 and promoted its expression by reducing the R-loop level. More, Hmga2 treatment delivered via the AAV system effectively decreased bone loss in aging mice and increased the serum bone turnover biomarkers and collagen remodeling. Conclusions: Our study demonstrates that Hmga2 acts as an activator of aging BMSCs, significantly promoting their osteogenic ability by eliminating the aging-induced DNA replication stress caused by R-loops. Our findings provide new insights into the mechanisms of aging-related bone loss, suggesting that Hmga2 may be a new strategy for alleviating the bone loss phenotype in aging individuals.
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Affiliation(s)
- Yangyang Cao
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China; (Y.C.); (Y.W.)
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Yantong Wang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China; (Y.C.); (Y.W.)
| | - Dengsheng Xia
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China; (Y.C.); (Y.W.)
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
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Pronina VV, Kostryukova LV, Ivanov SV, Tichonova EG, Archakov AI, Shumyantseva VV. Label-Free Electrochemical Cell-Based Biosensor for Toxicity Assay of Water-Soluble Form of Phosphatidylcholine. Biomedicines 2025; 13:996. [PMID: 40299676 PMCID: PMC12024718 DOI: 10.3390/biomedicines13040996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/17/2025] [Accepted: 04/18/2025] [Indexed: 05/01/2025] Open
Abstract
Background/Objectives: Our study brings a new method to properly evaluating drug efficacy at the non-invasive in vitro level. Methods: In this work, the electrochemical mediator-free and reagent-free analysis of cell lines based on the registration of electrochemical profiles of membrane proteins was developed. We studied the specificity of cell lines Wi-38 and HepG2 and the toxic effects of drugs on cell-on-electrode systems. Results: A linear dependence of the peak current on the concentration of cells applied to the electrode in the range from 1 × 105 to 6 × 105 cells/electrode was registered (R2 0.932 for Wi-38 and R2 0.912 for HepG2). The water-soluble form of phosphatidylcholine (wPC) nanoparticles recommended for atherosclerosis treatment and prevention of cardiovascular diseases did not show a toxic effect on the human fibroblast cells, Wi-38, or the human hepatocellular carcinoma cells, HepG2, at sufficiently high concentrations (such as 0.1-1 mg/mL). The antitumor drug doxorubicin, at concentrations of 3 and 10 μg/mL, showed a pronounced toxic effect on the tested cell lines, where the percentage of living cells was 50-55%. Conclusions: A comparative analysis of the cytotoxicity of wPC (0.1-1 mg/mL) and doxorubicin (3-10 μg/mL) on the cell lines Wi-38 and HepG2 using the MTT test and electrochemical approach for the registration of cells showed their clear adequacy.
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Affiliation(s)
- Veronica V. Pronina
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
| | - Lyubov V. Kostryukova
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
| | - Sergey V. Ivanov
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
| | - Elena G. Tichonova
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
| | - Alexander I. Archakov
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
| | - Victoria V. Shumyantseva
- Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; (V.V.P.); (L.V.K.); (S.V.I.); (E.G.T.); (A.I.A.)
- Faculty of Biomedicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia
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Du X, Pian H, Zhao D, Zhang Y, Wu X, He J, Chen L, Liu F, Yu D. Enhancing gut-ovary health in aged laying hens: the impact of dietary betaine supplementation. Poult Sci 2025; 104:104894. [PMID: 40020408 PMCID: PMC11910711 DOI: 10.1016/j.psj.2025.104894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 02/05/2025] [Accepted: 02/06/2025] [Indexed: 03/03/2025] Open
Abstract
The gut-ovary axis involves a complex interplay of various physiological and molecular mechanisms, which significantly impact poultry production and health. This study investigated the effects of betaine (Bet) on the gut-ovary axis of laying hens in aged laying hens. A total of 108 Hy-Line Brown hens, aged 500 days, were randomly divided into three groups (n = 36 per group) and fed diets containing 0, 1000, and 3000 mg/kg of Bet (designated as CON, l-Bet, and H-Bet, respectively) over a 42-day trial. The results indicated that dietary supplementation with Bet improved laying performance. Specifically, H-Bet Supplementation increased villus height (VH) and villus height/crypt depth ratio (VH/CD), and up-regulated the expression of Claudin-1 in the jejunal and ileal mucosa. Additionally, H-Bet enhanced the richness of Bacteroidetes and reduced Firmicutes/Bacterodietes ratio. LEfSe analysis revealed significant enrichment Eubacteriaceae, Merdibacter, Anaerorhabdus_furcosa_group, Syntrophococcus, and Clostridium_innocuum_group in Bet group. Transcriptome sequencing of small yellow follicles (SYFs) showed significant up-regulation of ATP6 and down-regulation of EGR1. KEGG enrichment analysis indicated that H-Bet influenced oxidative phosphorylation, peroxisome, and other pathways, with GESA was primarily enriched in oxidative phosphorylation, and MAPK signaling pathway. Furthermore, H-Bet supplementation increased SOD, CAT, Nrf2, NQO-1, and HO-1 expression in the jejunum, while only HO-1 expression was up-regulated in the ileum. In the ovary, H-Bet differentially affected GPX, and CAT expression. These results demonstrate that dietary supplementation with Bet improves intestinal and ovarian health in aged laying hens, likely due to enhanced antioxidant capacity and improved intestinal morphology.
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Affiliation(s)
- Xubin Du
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China; Joint International Research Laboratory of Animal Health and Food Safety of Ministry of Education & Single Molecule Biochemistry & Bioengineering Laboratory, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Huifang Pian
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Dong Zhao
- School of Animal Medical, Jiangsu Agri-animal Husbandry Vocational College, Taizhou, Jiangsu, 225300, PR China
| | - Yuchen Zhang
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Xinyue Wu
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Jiawen He
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Li Chen
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Fei Liu
- Joint International Research Laboratory of Animal Health and Food Safety of Ministry of Education & Single Molecule Biochemistry & Bioengineering Laboratory, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China
| | - Debing Yu
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China.
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Li Q, Xiao N, Zhang H, Liang G, Lin Y, Qian Z, Yang X, Yang J, Fu Y, Zhang C, Liu A. Systemic aging and aging-related diseases. FASEB J 2025; 39:e70430. [PMID: 40022602 DOI: 10.1096/fj.202402479rrr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 02/07/2025] [Accepted: 02/20/2025] [Indexed: 03/03/2025]
Abstract
Aging is a biological process along with systemic and multiple organ dysfunction. It is more and more recognized that aging is a systemic disease instead of a single-organ functional disorder. Systemic aging plays a profound role in multiple diseases including neurodegenerative diseases, cardiovascular diseases, and malignant diseases. Aged organs communicate with other organs and accelerate aging. Skeletal muscle, heart, bone marrow, skin, and liver communicate with each other through organ-organ crosstalk. The crosstalk can be mediated by metabolites including lipids, glucose, short-chain fatty acids (SCFA), inflammatory cytokines, and exosomes. Metabolic disorders including hyperglycemia, hyperinsulinemia, and hypercholesterolemia caused by chronic diseases accelerate hallmarks of aging. Systemic aging leads to the destruction of systemic hemostasis, causes the release of inflammatory cytokines, senescence-associated secretory phenotype (SASP), and the imbalance of microbiota composition. Released inflammatory factors further aggregate senescence, which promotes the aging of multiple solid organs. Targeting senescence or delaying aging is emerging as a critical health strategy for solving age-related diseases, especially in the old population. In the current review, we will delineate the mechanisms of organ crosstalk in systemic aging and age-related diseases to provide therapeutic targets for delaying aging.
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Affiliation(s)
- Qiao Li
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Nanyin Xiao
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Heng Zhang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Guangyu Liang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Yan Lin
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Zonghao Qian
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Xiao Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Jiankun Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Yanguang Fu
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Cuntai Zhang
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Anding Liu
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
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Jiang Q, Liu J, Huang S, Wang XY, Chen X, Liu GH, Ye K, Song W, Masters CL, Wang J, Wang YJ. Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances. Signal Transduct Target Ther 2025; 10:76. [PMID: 40059211 PMCID: PMC11891338 DOI: 10.1038/s41392-025-02145-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 11/29/2024] [Accepted: 01/15/2025] [Indexed: 05/13/2025] Open
Abstract
In the context of global ageing, the prevalence of neurodegenerative diseases and dementia, such as Alzheimer's disease (AD), is increasing. However, the current symptomatic and disease-modifying therapies have achieved limited benefits for neurodegenerative diseases in clinical settings. Halting the progress of neurodegeneration and cognitive decline or even improving impaired cognition and function are the clinically meaningful goals of treatments for neurodegenerative diseases. Ageing is the primary risk factor for neurodegenerative diseases and their associated comorbidities, such as vascular pathologies, in elderly individuals. Thus, we aim to elucidate the role of ageing in neurodegenerative diseases from the perspective of a complex system, in which the brain is the core and peripheral organs and tissues form a holistic network to support brain functions. During ageing, the progressive deterioration of the structure and function of the entire body hampers its active and adaptive responses to various stimuli, thereby rendering individuals more vulnerable to neurodegenerative diseases. Consequently, we propose that the prevention and treatment of neurodegenerative diseases should be grounded in holistic antiageing and rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach is a promising strategy to effectively prevent, pause or slow down the progression of neurodegenerative diseases.
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Affiliation(s)
- Qiu Jiang
- Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China
- Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China
| | - Jie Liu
- Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China
- Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China
| | - Shan Huang
- Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China
- Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China
| | - Xuan-Yue Wang
- Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China
| | - Xiaowei Chen
- Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China
- Brain Research Center, Third Military Medical University, Chongqing, China
| | - Guang-Hui Liu
- University of Chinese Academy of Sciences, Beijing, China
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Keqiang Ye
- Faculty of Life and Health Sciences, and Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Weihong Song
- Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province. Zhejiang Clinical Research Center for Mental Disorders, School of Mental Health and The Affiliated Kangning Hospital, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Colin L Masters
- The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
| | - Jun Wang
- Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
- Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China.
| | - Yan-Jiang Wang
- Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
- Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China.
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Xia X, Zhou K, An LY, Zhao M, Tian BL, Zhao JY, Zhou ZG, Tong Y. Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells. World J Stem Cells 2025; 17:96893. [DOI: 10.4252/wjsc.v17.i2.96893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 11/19/2024] [Accepted: 01/16/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Sepsis is a severe illness characterized by systemic and multiorgan reactive responses and damage. However, the impact of sepsis on the bone marrow, particularly on bone marrow mesenchymal stem cells (BMSCs), is less reported. BMSCs are critical stromal cells in the bone marrow microenvironment that maintain bone stability and hematopoietic homeostasis; however, the impairment caused by sepsis remains unknown.
AIM To investigate the effects of sepsis on BMSCs and the underlying mechanisms.
METHODS BMSCs were obtained from healthy donors and patients with sepsis. We compared the self-renewal capacity, differentiation potential, and hematopoietic supportive ability in vitro. Senescence of septic BMSCs was assessed using β-galactosidase staining, senescence-associated secretory phenotype, intracellular reactive oxygen species levels, and the expression of P16 and P21. Finally, the changes in septic BMSCs after nicotinamide adenine dinucleotide (NAD) treatment were evaluated.
RESULTS Septic BMSCs showed decreased proliferation and self-renewal, bias towards adipogenic differentiation, and weakened osteogenic differentiation. Additionally, hematopoietic supportive capacity declines in sepsis. The levels of aging markers were significantly higher in the septic BMSCs. After NAD treatment, the proliferation capacity of septic BMSCs showed a recovery trend, with increased osteogenic and hematopoietic supportive capacities. Sepsis resulted in decreased expression of sirtuin 3 (SIRT3) in BMSCs, whereas NAD treatment restored SIRT3 expression, enhanced superoxide dismutase enzyme activity, reduced intracellular reactive oxygen species levels, maintained mitochondrial stability and function, and ultimately rejuvenated septic BMSCs.
CONCLUSION Sepsis accelerates the aging of BMSCs, as evidenced by a decline in self-renewal and osteogenic capabilities, as well as weakened hematopoietic support functions. These deficiencies can be effectively reversed via the NAD/SIRT3/superoxide dismutase pathway.
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Affiliation(s)
- Xin Xia
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Kun Zhou
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Lin-Ying An
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Min Zhao
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Bin-Le Tian
- Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Jin-Yan Zhao
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Zhi-Gang Zhou
- Department of Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China
| | - Yin Tong
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
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Kuznetsov NV, Statsenko Y, Ljubisavljevic M. An Update on Neuroaging on Earth and in Spaceflight. Int J Mol Sci 2025; 26:1738. [PMID: 40004201 PMCID: PMC11855577 DOI: 10.3390/ijms26041738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/06/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Over 400 articles on the pathophysiology of brain aging, neuroaging, and neurodegeneration were reviewed, with a focus on epigenetic mechanisms and numerous non-coding RNAs. In particular, this review the accent is on microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training, or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which are especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific to neuroaging need to be validated to develop diagnostics and countermeasures.
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Affiliation(s)
- Nik V. Kuznetsov
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
| | - Yauhen Statsenko
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Milos Ljubisavljevic
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
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9
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Liu X, Zhao Y, Feng Y, Wang S, Luo A, Zhang J. Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body. Aging Dis 2025:AD.2024.1468. [PMID: 39965250 DOI: 10.14336/ad.2024.1468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/27/2025] [Indexed: 02/20/2025] Open
Abstract
Age-related diseases have emerged as a global concern as the population ages. Consequently, understanding the underlying causes of aging and exploring potential anti-aging interventions is imperative. In females, the ovaries serve as the principal organs responsible for ovulation and the production of female hormones. The aging ovaries are related to infertility, menopause, and associated menopausal syndromes, with menopause representing the culmination of ovarian aging. Current evidence indicates that ovarian aging may contribute to dysfunction across multiple organ systems, including, but not limited to, cognitive impairment, osteoporosis, and cardiovascular disease. Nevertheless, due to the widespread distribution of sex hormone receptors throughout the body, ovarian aging affects not only these specific organs but also influences a broader spectrum of age-related diseases in women. Despite this, the impact of ovarian aging on overall age-related diseases has been largely neglected. This review provides a thorough summary of the impact of ovarian aging on age-related diseases, encompassing the nervous, circulatory, locomotor, urinary, digestive, respiratory, and endocrine systems. Additionally, we have outlined prospective therapeutic approaches for addressing both ovarian aging and age-related diseases, with the aim of mitigating their impacts and preserving women's fertility, physical health, and psychological well-being.
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Affiliation(s)
- Xingyu Liu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuanqu Zhao
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yanzhi Feng
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shixuan Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Aiyue Luo
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jinjin Zhang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China
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10
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Li C, Yuan Y, Jia Y, Zhou Q, Wang Q, Jiang X. Cellular senescence: from homeostasis to pathological implications and therapeutic strategies. Front Immunol 2025; 16:1534263. [PMID: 39963130 PMCID: PMC11830604 DOI: 10.3389/fimmu.2025.1534263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence and cancer is complex and multifaceted, senescence can both promote and inhibit tumor progression through various mechanisms. M6A methylation modification regulates the aging process of cells and tissues by modulating senescence-related genes. In this review, we comprehensively discuss the characteristics of cellular senescence, the signaling pathways regulating senescence, the biomarkers of senescence, and the mechanisms of anti-senescence drugs. Notably, this review also delves into the complex interactions between senescence and cancer, emphasizing the dual role of the senescent microenvironment in tumor initiation, progression, and treatment. Finally, we thoroughly explore the function and mechanism of m6A methylation modification in cellular senescence, revealing its critical role in regulating gene expression and maintaining cellular homeostasis. In conclusion, this review provides a comprehensive perspective on the molecular mechanisms and biological significance of cellular senescence and offers new insights for the development of anti-senescence strategies.
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Affiliation(s)
- Chunhong Li
- Department of Oncology, Suining Central Hospital, Suining, Sichuan, China
| | - Yixiao Yuan
- Department of Medicine, Health Cancer Center, University of Florida, Gainesville, FL, United States
| | - YingDong Jia
- Gastrointestinal Surgical Unit, Suining Central Hospital, Suining, Sichuan, China
| | - Qiang Zhou
- Department of Oncology, Suining Central Hospital, Suining, Sichuan, China
| | - Qiang Wang
- Gastrointestinal Surgical Unit, Suining Central Hospital, Suining, Sichuan, China
| | - Xiulin Jiang
- Department of Medicine, Health Cancer Center, University of Florida, Gainesville, FL, United States
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11
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Guo X, Dai X. A complex systems approach to mosaic loss of the Y chromosome. GeroScience 2025; 47:631-651. [PMID: 39680277 PMCID: PMC11872822 DOI: 10.1007/s11357-024-01468-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 12/05/2024] [Indexed: 12/17/2024] Open
Abstract
Mosaic loss of Y chromosome (mLOY) is an acquired condition wherein a sizeable proportion of an organ's cells have lost their Y. Large-scale cohort studies have shown that mLOY is age-dependent and a strong risk factor for all-cause mortality and adverse outcomes of age-related diseases. Emerging multi-omics approaches that combine gene expression, epigenetic and mutational profiling of human LOY cell populations at single-cell levels, and contemporary work in in vitro cell and preclinical mouse models have provided important clues into how mLOY mechanistically contributes to disease onset and progression. Despite these advances, what has been missing is a system-level insight into mLOY. By integrating the most recent advances in wide-ranging aspects of mLOY research, we summarize a unified model to understanding the cause and consequence of mLOY at the molecular, cellular, and organismal levels. This model, referred to as the "Unstable Y Cascade model," states that (i) the rise and expansion of LOY result from interaction by the inherently unstable Y, germline genetic and epigenetic variants, and numerous cell-intrinsic and external factors; (ii) LOY initiates genomic, epigenomic, and transcriptomic alterations in X and autosomes, thereafter induces a cascade of tissue-specific cellular alterations that contribute locally to the onset and progression of diseases; and (iii) LOY cells exert paracrine effects to non-LOY cells, thereby amplifying LOY-associated pathological signaling cascades to remote non-LOY cells. This new model has implications in the development of therapeutic interventions that could prevent or delay age-related diseases via mitigating mLOY burden.
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Affiliation(s)
- Xihan Guo
- School of Life Sciences, Yunnan Normal University, Kunming, 650500, Yunnan, China.
| | - Xueqin Dai
- Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China
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12
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Fuerlinger A, Stockner A, Sedej S, Abdellatif M. Caloric restriction and its mimetics in heart failure with preserved ejection fraction: mechanisms and therapeutic potential. Cardiovasc Diabetol 2025; 24:21. [PMID: 39827109 PMCID: PMC11742808 DOI: 10.1186/s12933-024-02566-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025] Open
Abstract
The global increase in human life expectancy, coupled with an unprecedented rise in the prevalence of obesity, has led to a growing clinical and socioeconomic burden of heart failure with preserved ejection fraction (HFpEF). Mechanistically, the molecular and cellular hallmarks of aging are omnipresent in HFpEF and are further exacerbated by obesity and associated metabolic diseases. Conversely, weight loss strategies, particularly caloric restriction, have shown promise in improving health status in patients with HFpEF and are considered the gold standard for promoting longevity and healthspan (disease-free lifetime) in model organisms. In this review, we implicate fundamental mechanisms of aging in driving HFpEF and elucidate how caloric restriction mitigates the disease progression. Furthermore, we discuss the potential for pharmacologically mimicking the beneficial effects of caloric restriction in HFpEF using clinically approved and emerging caloric restriction mimetics. We surmise that these compounds could offer novel therapeutic avenues for HFpEF and alleviate the challenges associated with the implementation of caloric restriction and other lifestyle modifications to reduce the burden of HFpEF at a population level.
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Affiliation(s)
- Alexander Fuerlinger
- Department of Cardiology, Medical University of Graz, 8036, Graz, Austria
- BioTechMed-Graz, 8010, Graz, Austria
| | - Alina Stockner
- Department of Cardiology, Medical University of Graz, 8036, Graz, Austria
| | - Simon Sedej
- Department of Cardiology, Medical University of Graz, 8036, Graz, Austria
- BioTechMed-Graz, 8010, Graz, Austria
- Faculty of Medicine, University of Maribor, 2000, Maribor, Slovenia
| | - Mahmoud Abdellatif
- Department of Cardiology, Medical University of Graz, 8036, Graz, Austria.
- BioTechMed-Graz, 8010, Graz, Austria.
- Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805, Villejuif, France.
- Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris, 75006, France.
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13
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Yin Z, Tian L, Kou W, Cao G, Wang L, Xia Y, Lin Y, Tang S, Zhang J, Yang H. Xiyangshen Sanqi Danshen granules attenuated D-gal-induced C57BL/6J mouse aging through the AMPK/SIRT1 signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 136:156213. [PMID: 39603038 DOI: 10.1016/j.phymed.2024.156213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 10/22/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Aging is a pressing global concern and is frequently accompanied by the emergence of many chronic diseases. Xiyangshen Sanqi Danshen granules (XSD) have antioxidant, anti-inflammatory and anti-fatigue functions, but the mechanism of their anti-aging effects is not clear. METHODS This study elucidated the anti-aging mechanism and potentially active ingredients of XSD by performing transcriptomic analysis and network pharmacological analysis in a D-galactose (D-gal)-induced C57BL/6J mouse aging model. RESULTS XSD improved learning and memory abilities while enhanced motor function in D-gal-induced aging mice, as shown by Morris water maze, passive avoidance test, and rotating rod test results. Additionally, XSD significantly increased the vascular pulse wave velocity (PWV), β-stiffness index and pressure strain elastic coefficient (EP), decreased carotid distensibility (CD) and decreased the expression levels of P53 and 8-OHdG in the common carotid arteries of D-gal mice. Transcriptome sequencing analysis identified that the AMPK/SIRT1 signaling pathway is the potential mechanism by which XSD attenuates aging. XSD also increased the protein levels of Ki67, AMPK, SIRT1 and the nuclear translocation of Nrf2 while decreased the protein levels of P21, P53, IL-18, 8-OHdG, nitrotyrosine, and COX-2 and the nuclear translocation of NF-κB p65 in the brains of D-gal-induced mice. The administration of the AMPK inhibitor and SIRT1 inhibitor hindered the anti-aging effect of XSD, as indicated by an elevation of 8-OHdG, COX-2, and nuclear translocation of NF-κB p65 ; and a decrease of Ki67 and the nuclear translocation of Nrf2. Network pharmacological analysis revealed that the potential active ingredients of XSD were quercetin, kaempferol, tanshinone IIA, isorhamnetin, ginsenoside F2, and cryptotanshinone. CONCLUSION Collectively, XSD mitigated D-gal-induced aging in C57BL/6J mice through enhancing the AMPK/SIRT1 signaling pathway. This research provides potential drugs for anti-aging and also promotes the usage of the anti-aging effect of XSD.
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Affiliation(s)
- Zhiru Yin
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Liangliang Tian
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China
| | - Wenzhuo Kou
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Guangzhao Cao
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Liju Wang
- Zhangzhou Pien Tze Huang Pharmaceutical Co.,Ltd, Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou 363000, China
| | - Yufa Xia
- Zhangzhou Pien Tze Huang Pharmaceutical Co.,Ltd, Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou 363000, China
| | - Yidong Lin
- Zhangzhou Pien Tze Huang Pharmaceutical Co.,Ltd, Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou 363000, China
| | - Shihuan Tang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Jingjing Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Chinese Institute for Brain Research, Beijing 102206, China.
| | - Hongjun Yang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
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14
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Alugoju P, Palanisamy CP, Anthikapalli NVA, Jayaraman S, Prasanskulab A, Chuchawankul S, Dyavaiah M, Tencomnao T. Exploring the anti-aging potential of natural products and plant extracts in budding yeast Saccharomyces cerevisiae: A review. F1000Res 2024; 12:1265. [PMID: 39822944 PMCID: PMC11736113 DOI: 10.12688/f1000research.141669.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/10/2024] [Indexed: 01/19/2025] Open
Abstract
Historically, plant derived natural products and their crude extracts have been used to treat a wide range of ailments across the world. Biogerontology research aims to explore the molecular basis of aging and discover new anti-aging therapeutic compounds or formulations to combat the detrimental effects of aging and promote a healthy life span. The budding yeast Saccharomyces cerevisiae has been, and continues to be, an indispensable model organism in the field of biomedical research for discovering the molecular basis of aging S. cerevisiae has preserved nutritional signaling pathways (such as the target of rapamycin (TOR)-Sch9 and the Ras-AC-PKA (cAMP-dependent protein kinase) pathways, and shows two distinct aging paradigms chronological life span (CLS) and replicative life span (RLS). This review explores the anti-aging properties of natural products, predominantly derived from plants, and phytoextracts using S. cerevisiae as a model organism.
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Affiliation(s)
- Phaniendra Alugoju
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Chella Perumal Palanisamy
- Department of Chemical Technology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | | | - Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, Tamilnadu, 600077, India
| | - Anchalee Prasanskulab
- College of Public Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Siriporn Chuchawankul
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Madhu Dyavaiah
- Department of Biochemistry and Molecular Biology, Pondicherry University (A Central University), Puducherry, 605 014, India
| | - Tewin Tencomnao
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
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15
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Alugoju P, Palanisamy CP, Anthikapalli NVA, Jayaraman S, Prasanskulab A, Chuchawankul S, Dyavaiah M, Tencomnao T. Exploring the anti-aging potential of natural products and plant extracts in budding yeast Saccharomyces cerevisiae: A review. F1000Res 2024; 12:1265. [PMID: 39822944 PMCID: PMC11736113 DOI: 10.12688/f1000research.141669.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/10/2024] [Indexed: 05/11/2025] Open
Abstract
Historically, plant derived natural products and their crude extracts have been used to treat a wide range of ailments across the world. Biogerontology research aims to explore the molecular basis of aging and discover new anti-aging therapeutic compounds or formulations to combat the detrimental effects of aging and promote a healthy life span. The budding yeast Saccharomyces cerevisiae has been, and continues to be, an indispensable model organism in the field of biomedical research for discovering the molecular basis of aging S. cerevisiae has preserved nutritional signaling pathways (such as the target of rapamycin (TOR)-Sch9 and the Ras-AC-PKA (cAMP-dependent protein kinase) pathways, and shows two distinct aging paradigms chronological life span (CLS) and replicative life span (RLS). This review explores the anti-aging properties of natural products, predominantly derived from plants, and phytoextracts using S. cerevisiae as a model organism.
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Affiliation(s)
- Phaniendra Alugoju
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Chella Perumal Palanisamy
- Department of Chemical Technology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | | | - Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, Tamilnadu, 600077, India
| | - Anchalee Prasanskulab
- College of Public Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Siriporn Chuchawankul
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Madhu Dyavaiah
- Department of Biochemistry and Molecular Biology, Pondicherry University (A Central University), Puducherry, 605 014, India
| | - Tewin Tencomnao
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
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16
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Chen P, Wu L, Lei J, Chen F, Feng L, Liu G, Zhou B. The ellagitannin metabolite urolithin C attenuated cognitive impairment by inhibiting neuroinflammation via downregulation of MAPK/NF-kB signaling pathways in aging mice. Int Immunopharmacol 2024; 142:113151. [PMID: 39303538 DOI: 10.1016/j.intimp.2024.113151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 09/09/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
The current study aimed to evaluate the preventive effects of urolithin C (Uro C), a gut microbial metabolite of ellagitannins on D-galactose (D-gal)-induced brain damage during the aging process and to elucidate the underlying mechanisms. In our study, the protective effect of Uro C on D-gal-induced BV2 microglia cell-mediated neuroinflammation damage in primary cortical neurons in vitro was confirmed. The results in an aging model in vivo induced by D-gal demonstrated that Uro C prevented D-gal-induced memory impairment, long-term potentiation (LTP) damage, and synaptic dysfunction through behavioral, electrophysiological, and histological examinations. Additionally, amyloidogenesis was observed in the central nervous system. The findings indicated that Uro C exhibited a preventive effect on the D-gal-induced elevation of β-amyloid (1-42 specific) (Aβ1-42) accumulation, APP levels, ABCE1 levels, and the equilibrium of the cholinergic system in the aging mouse brain. Moreover, Uro C demonstrated downregulation of D-gal-induced glial overactivation through inhibition of the MAPK/NF-kB pathway. This resulted in the regulation of inflammatory mediators and cytokines, including iNOS, IL-6, IL-1β, and TNF-ɑ, in the mouse brain and BV2 microglial cells. Taken together, our results suggested that Uro C treatment could effectively mitigate the D-gal-induced memory impairment and amyloidogenesis, and the underlying mechanism might be tightly related to the improvement of neuroinflammation by suppressing the MAPK/NF-kB pathway, indicating Uro C might be an alternative and promising agent for the treatment of aging and age-associated brain diseases.
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Affiliation(s)
- Peng Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei.
| | - Lining Wu
- Department of Pharmacy, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi
| | - Jiexin Lei
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Fuchao Chen
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, PR China
| | - Lihua Feng
- School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, PR China
| | - Gang Liu
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei
| | - Benhong Zhou
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei
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17
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Intharuksa A, Kuljarusnont S, Sasaki Y, Tungmunnithum D. Flavonoids and Other Polyphenols: Bioactive Molecules from Traditional Medicine Recipes/Medicinal Plants and Their Potential for Phytopharmaceutical and Medical Application. Molecules 2024; 29:5760. [PMID: 39683916 DOI: 10.3390/molecules29235760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/25/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
Currently, natural bioactive ingredients and/or raw materials are of significant interest to scientists around the world. Flavonoids and other polyphenols are a major group of phytochemicals that have been researched and noted as bioactive molecules. They offer several pharmacological and medical benefits. This current review aims to (1) illustrate their benefits for human health, such as antioxidant, anti-aging, anti-cancer, anti-inflammatory, anti-microbial, cardioprotective, neuroprotective, and UV-protective effects, and also (2) to perform a quality evaluation of traditional medicines for future application. Consequently, keywords were searched on Scopus, Google Scholar, and PubMed so as to search for related publications. Then, those publications were carefully checked in order to find current and non-redundant studies that matched the objective of this review. According to this review, researchers worldwide are very interested in discovering the potential of flavonoids and other polyphenols, used in traditional medicines and taken from medicinal plants, in relation to medical and pharmaceutical applications. Many studies focus on the health benefits of flavonoids and other polyphenols have been tested using in silico, in vitro, and in vivo models. However, few studies have been carried out using clinical trials that have trustworthy subject sizes and are in accordance with clinical practice guidelines. Additionally, interesting research directions and perspectives for future studies are highlighted in this work.
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Affiliation(s)
- Aekkhaluck Intharuksa
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Sompop Kuljarusnont
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Yohei Sasaki
- Division of Pharmaceutical Sciences, Graduate School of Medical Plant Sciences, Kanazawa University, Kanazawa 920-1192, Japan
| | - Duangjai Tungmunnithum
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
- Le Studium Institute for Advanced Studies, 1 Rue Dupanloup, 45000 Orléans, France
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18
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Chen P, Zhang Z, Lei J, Zhu J, Liu G. Ellagitannin Component Punicalin Ameliorates Cognitive Dysfunction, Oxidative Stress, and Neuroinflammation via the Inhibition of cGAS-STING Signaling in the Brain of an Aging Mouse Model. Phytother Res 2024; 38:5690-5712. [PMID: 39313488 DOI: 10.1002/ptr.8343] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/20/2024] [Accepted: 08/27/2024] [Indexed: 09/25/2024]
Abstract
Despite remarkable breakthroughs in pharmacotherapy, many potential therapies for aging remain unexplored. Punicalin (PUN), an ellagitannin component, exerts anti-inflammatory, antioxidant, and anti-apoptotic effects. This study investigated the beneficial effects of PUN against age-related brain damage in mice and explored the underlying mechanisms. We validated the protective effects of PUN against D-galactose (D-gal)-induced neuroinflammation and subsequent neuronal damage in BV2 microglia and N2a cells, respectively, in vitro. In vivo experiments were conducted on mice that were administered an 8-week regimen of intraperitoneal injections of D-gal at a dosage of 150 mg/kg/day, concurrently with oral gavage of PUN at the same dose. PUN inhibited the production of D-gal-induced inflammatory cytokines (iNOS, COX2, TNF-α, IL-6, IL-2, and IL-1β) in BV2 cells and conferred protection to N2a cells against synaptic damage mediated by BV2 microglia-induced neuroinflammation. The in vivo findings revealed that PUN considerably improved memory and learning deficits, reduced MDA levels, enhanced GSH-Px, CAT, and SOD activities, and modulated the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the secretion of SASP factors (ICAM-1, PAI-1, MMP-3, and MMP-9), decreased microglial activation, and reduced astrocytosis. Additionally, PUN suppressed the expression of cGAS, p-STING, p-TBK1, p-p65, and p-IRF3 in aging mouse brains and cultured BV2 microglia. In conclusion, PUN improved cognitive dysfunction in aging mice through antioxidant and anti-inflammatory mechanisms via inhibition of the cGAS-STING pathway, suggesting that it can be a promising therapeutic agent for brain aging and aging-related diseases.
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Affiliation(s)
- Peng Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Zhongyuan Zhang
- Department of Pharmacy, Wuhan Red Cross Hospital, Wuhan, People's Republic of China
| | - Jiexin Lei
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Jun Zhu
- Department of Pharmacy, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Gang Liu
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
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19
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Jackson MJ. Reactive oxygen species in age-related musculoskeletal decline: implications for nutritional intervention. Proc Nutr Soc 2024:1-9. [PMID: 39512110 DOI: 10.1017/s0029665124004877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Musculoskeletal disorders and age-related musculoskeletal decline are major contributors to the burden of ill health seen in older subjects. Despite this increased burden, these chronic disorders of old age receive a relatively small proportion of national research funds. Much has been learned about fundamental processes involved in ageing from basic science research and this is leading to identification of key pathways that mediate ageing which may help the search for interventions to reduce age-related musculoskeletal decline. This short review will focus on the role of reactive oxygen species in age-related skeletal muscle decline and on the implications of this work for potential nutritional interventions in sarcopenia. The key physiological role of reactive oxygen species is now known to be in mediating redox signalling in muscle and other tissues and ageing leads to disruption of such pathways. In muscle, this is reflected in an age-related attenuation of specific adaptations and responses to contractile activity that impacts the ability of skeletal muscle from ageing individuals to respond to exercise. These pathways provides potential targets for identification of logical interventions that may help maintain muscle mass and function during ageing.
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Affiliation(s)
- Malcolm J Jackson
- MRC-Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
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20
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Liu Z, Xie W, Li H, Liu X, Lu Y, Lu B, Deng Z, Li Y. Novel perspectives on leptin in osteoarthritis: Focus on aging. Genes Dis 2024; 11:101159. [PMID: 39229323 PMCID: PMC11369483 DOI: 10.1016/j.gendis.2023.101159] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 09/10/2023] [Accepted: 09/16/2023] [Indexed: 09/05/2024] Open
Abstract
Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration, subchondral sclerosis, synovitis, and osteophyte formation. OA is associated with disability and impaired quality of life, particularly among the elderly. Leptin, a 16-kD non-glycosylated protein encoded by the obese gene, is produced on a systemic and local basis in adipose tissue and the infrapatellar fat pad located in the knee. The metabolic mechanisms employed by leptin in OA development have been widely studied, with attention being paid to aging as a corroborative risk factor for OA. Hence, in this review, we have attempted to establish a potential link between leptin and OA, by focusing on aging-associated mechanisms and proposing leptin as a potential diagnostic and therapeutic target in aging-related mechanisms of OA that may provide fruitful guidance and emphasis for future research.
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Affiliation(s)
- Zimo Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410083, China
| | - Wenqing Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Hengzhen Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Xu Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yao Lu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410083, China
| | - Bangbao Lu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Zhenhan Deng
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Yusheng Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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21
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Hartinger R, Singh K, Leverett J, Djabali K. Enhancing Cellular Homeostasis: Targeted Botanical Compounds Boost Cellular Health Functions in Normal and Premature Aging Fibroblasts. Biomolecules 2024; 14:1310. [PMID: 39456243 PMCID: PMC11506649 DOI: 10.3390/biom14101310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/06/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
The human skin, the body's largest organ, undergoes continuous renewal but is significantly impacted by aging, which impairs its function and leads to visible changes. This study aimed to identify botanical compounds that mimic the anti-aging effects of baricitinib, a known JAK1/2 inhibitor. Through in silico screening of a botanical compound library, 14 potential candidates were identified, and 7 were further analyzed for their effects on cellular aging. The compounds were tested on both normal aged fibroblasts and premature aging fibroblasts derived from patients with Hutchinson-Gilford Progeria Syndrome (HGPS). Results showed that these botanical compounds effectively inhibited the JAK/STAT pathway, reduced the levels of phosphorylated STAT1 and STAT3, and ameliorated phenotypic changes associated with cellular aging. Treatments improved cell proliferation, reduced senescence markers, and enhanced autophagy without inducing cytotoxicity. Compounds, such as Resveratrol, Bisdemethoxycurcumin, Pinosylvin, Methyl P-Hydroxycinnamate, cis-Pterostilbene, and (+)-Gallocatechin, demonstrated significant improvements in both control and HGPS fibroblasts. These findings suggest that these botanical compounds have the potential to mitigate age-related cellular alterations, offering promising strategies for anti-aging therapies, particularly for skin health. Further in vivo studies are warranted to validate these results and explore their therapeutic applications.
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Affiliation(s)
- Ramona Hartinger
- Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany;
| | - Khushboo Singh
- Amway Corporation, Innovation and Science, 7575 Fulton Street East, Ada, MI 49355, USA
| | - Jesse Leverett
- Amway Corporation, Innovation and Science, 7575 Fulton Street East, Ada, MI 49355, USA
| | - Karima Djabali
- Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany;
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22
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Du J, Chen F, Du C, Zhao W, Chen Z, Ding Z, Zhou M. Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair. Cell Death Discov 2024; 10:434. [PMID: 39394181 PMCID: PMC11470136 DOI: 10.1038/s41420-024-02201-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 09/21/2024] [Accepted: 09/30/2024] [Indexed: 10/13/2024] Open
Abstract
DNA damage is considered to be a potentially unifying driver of ageing, and the stalling of DNA damage repair accelerates the cellular senescence. However, augmenting DNA repair has remained a great challenge due to the intricate repair mechanisms specific for multiple types of lesions. Herein, we miniaturized our modified detecting system for homologous recombination (HR) into a 96-well-based platform and performed a high-throughput chemical screen for FDA-approved drugs. We uncovered that amodiaquine could significantly augment HR repair at the noncytotoxic concentration. Further experiments demonstrated that amodiaquine remarkably suppressed stress-induced premature cellular senescence (SIPS), as evidenced by senescence-associated beta-galactosidase (SA-β-gal) staining or senescence-related markers p21WAF1 and p16ink4a, and the expression of several cytokines. Mechanistic studies revealed that the stimulation of HR repair by amodiaquine might be mostly attributable to the promotion of SIRT1 at the transcriptional level. Additionally, SIRT1 depletion abolished the amodiaquine-mediated effects on DNA repair and cellular senescence, indicating that amodiaquine delayed the onset of SIPS via a SIRT1-dependent pathway. Taken together, this experimental approach paved the way for the identification of compounds that augment HR activity, which could help to underscore the therapeutic potential of targeting DNA repair for treating aging-related diseases.
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Affiliation(s)
- Jie Du
- Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, Guangdong, China
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Fuqiang Chen
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Chenghong Du
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Wenna Zhao
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Zihan Chen
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhenhua Ding
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
| | - Meijuan Zhou
- Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, Guangdong, China.
- Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
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23
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Bonnes SLR, Strauss T, Palmer AK, Hurt RT, Island L, Goshen A, Wang LYT, Kirkland JL, Bischof E, Maier AB. Establishing healthy longevity clinics in publicly funded hospitals. GeroScience 2024; 46:4217-4223. [PMID: 38512582 PMCID: PMC11336016 DOI: 10.1007/s11357-024-01132-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 03/11/2024] [Indexed: 03/23/2024] Open
Abstract
Healthy longevity medicine integrates geroscience and other disciplines into clinical settings, aiming to optimize health throughout one's lifespan. Multiple factors have led to increased consumer engagement, with private clinics currently meeting the demand for guidance to improve healthy longevity. The establishment of healthy longevity clinics in publicly funded hospitals is a significant development, making longevity-focused healthcare more accessible. These clinics rely on multidisciplinary teams of physicians and allied health professionals. Diagnostics involve comprehensive evaluations of medical history, physical examinations, and various clinical tests to detect early signs of age-related functional decline. Interventions in healthy longevity medicine encompass lifestyle modifications, supplements, repurposed drugs, and social and environmental interventions. Collaboration with research institutions and industry partners is crucial for advancing healthy longevity medicine and creating standardized protocols. In this article, we review the process of creating healthy longevity clinics in public hospitals to ensure the best possible care for individuals pursuing healthy longevity.
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Affiliation(s)
| | - Tzipora Strauss
- Sheba Longevity Center, Sheba Medical Center, Tel Hashomer, Israel
- Tel Aviv Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Ryan T Hurt
- Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Louis Island
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117456, Singapore
- Centre for Healthy Longevity, @AgeSingapore, National University Health System (NUHS), Singapore, Singapore
| | - Abigail Goshen
- Sheba Longevity Center, Sheba Medical Center, Tel Hashomer, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Laureen Y T Wang
- Centre for Healthy Longevity, @AgeSingapore, National University Health System (NUHS), Singapore, Singapore
- Well Programme, Alexandra Hospital, National University Health System (NUHS), Singapore, Singapore
| | | | - Evelyne Bischof
- Sheba Longevity Center, Sheba Medical Center, Tel Hashomer, Israel
- Tel Aviv Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Renji Hospital of the Jiaotong University School of Medicine, Department of Oncology and Clinical Cancer Center, State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Andrea B Maier
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117456, Singapore
- Centre for Healthy Longevity, @AgeSingapore, National University Health System (NUHS), Singapore, Singapore
- Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands
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24
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Jang D, Shin J, Shim E, Ohtani N, Jeon OH. The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review. Aging Cell 2024; 23:e14315. [PMID: 39148278 PMCID: PMC11464129 DOI: 10.1111/acel.14315] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/24/2024] [Accepted: 08/06/2024] [Indexed: 08/17/2024] Open
Abstract
The intricate interplay between cellular senescence and alterations in the gut microbiome emerges as a pivotal axis in the aging process, increasingly recognized for its contribution to systemic inflammation, physiological decline, and predisposition to age-associated diseases. Cellular senescence, characterized by a cessation of cell division in response to various stressors, induces morphological and functional changes within tissues. The complexity and heterogeneity of senescent cells, alongside the secretion of senescence-associated secretory phenotype, exacerbate the aging process through pro-inflammatory pathways and influence the microenvironment and immune system. Concurrently, aging-associated changes in gut microbiome diversity and composition contribute to dysbiosis, further exacerbating systemic inflammation and undermining the integrity of various bodily functions. This review encapsulates the burgeoning research on the reciprocal relationship between cellular senescence and gut dysbiosis, highlighting their collective impact on age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and osteoarthritis. It also explores the potential of modulating the gut microbiome and targeting cellular senescence as innovative strategies for healthy aging and mitigating the progression of aging-related conditions. By exploring targeted interventions, including the development of senotherapeutic drugs and probiotic therapies, this review aims to shed light on novel therapeutic avenues. These strategies leverage the connection between cellular senescence and gut microbiome alterations to advance aging research and development of interventions aimed at extending health span and improving the quality of life in the older population.
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Affiliation(s)
- Dong‐Hyun Jang
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Ji‐Won Shin
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Eunha Shim
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Naoko Ohtani
- Department of PathophysiologyOsaka Metropolitan University Graduate School of MedicineOsakaJapan
| | - Ok Hee Jeon
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
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25
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Liu Y, Fang M, Tu X, Mo X, Zhang L, Yang B, Wang F, Kim YB, Huang C, Chen L, Fan S. Dietary Polyphenols as Anti-Aging Agents: Targeting the Hallmarks of Aging. Nutrients 2024; 16:3305. [PMID: 39408272 PMCID: PMC11478989 DOI: 10.3390/nu16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/20/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Methods: Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous biological activities, including antioxidant effects, free radical scavenging, neuroprotection, and anti-aging properties. These compounds are generally safe and effective in potentially slowing aging and preventing age-related disorders. Conclusions: The review encourages the development of novel therapeutic strategies using dietary polyphenols to create holistic anti-aging therapies and nutritional supplements.
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Affiliation(s)
- Ying Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Minglv Fang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xiaohui Tu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xueying Mo
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Lu Zhang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Binrui Yang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Feijie Wang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Young-Bum Kim
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Cheng Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Liang Chen
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Shengjie Fan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
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26
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Tam LM, Bushnell T. Deciphering the aging process through single-cell cytometric technologies. Cytometry A 2024; 105:621-638. [PMID: 38847116 PMCID: PMC12147454 DOI: 10.1002/cyto.a.24852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 04/26/2024] [Accepted: 05/10/2024] [Indexed: 03/20/2025]
Abstract
The advent of single-cell cytometric technologies, in conjunction with advances in single-cell biology, has significantly propelled forward the field of geroscience, enhancing our comprehension of the mechanisms underlying age-related diseases. Given that aging is a primary risk factor for numerous chronic health conditions, investigating the dynamic changes within the physiological landscape at the granularity of single cells is crucial for elucidating the molecular foundations of biological aging. Utilizing hallmarks of aging as a conceptual framework, we review current literature to delineate the progression of single-cell cytometric techniques and their pivotal applications in the exploration of molecular alterations associated with aging. We next discuss recent advancements in single-cell cytometry in terms of the development in instrument, software, and reagents, highlighting its promising and critical role in driving future breakthrough discoveries in aging research.
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Affiliation(s)
- Lok Ming Tam
- Center for Advanced Research Technologies, University of Rochester Medical Center, Rochester, New York, USA
| | - Timothy Bushnell
- Center for Advanced Research Technologies, University of Rochester Medical Center, Rochester, New York, USA
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27
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Yu L, Russ AN, Algamal M, Abedin MJ, Zhao Q, Miller MR, Perle SJ, Kastanenka KV. Slow wave activity disruptions and memory impairments in a mouse model of aging. Neurobiol Aging 2024; 140:12-21. [PMID: 38701647 PMCID: PMC11188680 DOI: 10.1016/j.neurobiolaging.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 03/29/2024] [Accepted: 04/17/2024] [Indexed: 05/05/2024]
Abstract
The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5-1 Hz) and delta (1-4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively. SWA disruptions might lead to memory disturbances often experienced by older adults. We conducted behavioral tests in young and older C57BL/6 J mice. SWA was monitored using wide-field imaging with voltage sensors. Cell-specific calcium imaging was used to monitor the activity of excitatory and inhibitory neurons in these mice. Older mice exhibited impairments in working memory but not memory consolidation. Voltage-sensor imaging revealed aberrant synchronization of neuronal activity in older mice. Notably, we found older mice exhibited no significant alterations in slow oscillations, whereas there was a significant increase in delta power compared to young mice. Calcium imaging revealed hypoactivity in inhibitory neurons of older mice. Combined, these results suggest that neural activity disruptions might correlate with aberrant memory performance in older mice.
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Affiliation(s)
- Lu Yu
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Alyssa N Russ
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Moustafa Algamal
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Md Joynal Abedin
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Qiuchen Zhao
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Morgan R Miller
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Stephen J Perle
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Ksenia V Kastanenka
- Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
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28
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Zhang M, Hu T, Ma T, Huang W, Wang Y. Epigenetics and environmental health. Front Med 2024; 18:571-596. [PMID: 38806988 DOI: 10.1007/s11684-023-1038-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 10/15/2023] [Indexed: 05/30/2024]
Abstract
Epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling, and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological processes. In recent years, accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth, development, and diseases of individuals by affecting chromatin activity and regulating gene expression. Environmental exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders, aging, cardiovascular disease, Alzheimer's disease, cancers, and so on. However, epigenetic modifications are reversible. The use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease therapy. Here, we provide an overview of the role of epigenetics in various diseases. Furthermore, we summarize the mechanism of epigenetic alterations induced by different environmental exposures, the influence of different environmental exposures, and the crosstalk between environmental variation epigenetics, and genes that are implicated in the body's health. However, the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical treatments. We discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.
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Affiliation(s)
- Min Zhang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ting Hu
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Tianyu Ma
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China
| | - Wei Huang
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
| | - Yan Wang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
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Mironov S, Borysova O, Morgunov I, Zhou Z, Moskalev A. A Framework for an Effective Healthy Longevity Clinic. Aging Dis 2024:AD.2024.0328-1. [PMID: 38607731 DOI: 10.14336/ad.2024.0328-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 07/15/2024] [Indexed: 09/11/2024] Open
Abstract
In the context of an aging global population and the imperative for innovative healthcare solutions, the concept of longevity clinics emerges as a timely and vital area of exploration. Unlike traditional medical facilities, longevity clinics offer a unique approach to preclinical prevention, focusing on "prevention of prevention" through the utilization of aging clocks and biomarkers from healthy individuals. This article presents a comprehensive overview of longevity clinics, encompassing descriptions of existing models, the development of a proposed framework, and insights into biomarkers, wearable devices, and therapeutic interventions. Additionally, economic justifications for investing in longevity clinics are examined, highlighting the significant growth potential of the global biotechnology market and its alignment with the goals of achieving active longevity. Anchored by an Analytical Center, the proposed framework underscores the importance of data-driven decision-making and innovation in promoting prolonged and enhanced human life. At present, there is no universally accepted standard model for longevity clinics. This absence highlights the need for additional research and ongoing improvements in this field. Through a synthesis of scientific research and practical considerations, this article aims to stimulate further discussion and innovation in the field of longevity clinics, ultimately contributing to the advancement of healthcare practices aimed at extending and enhancing human life.
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Affiliation(s)
- Sergey Mironov
- Longaevus Technologies LTD, London, United Kingdom
- Human and health division, DEKRA Automobil GmbH, Chemnitz, Germany
| | | | | | - Zhongjun Zhou
- School of Biomedical Sciences, University of Hong Kong, Hong Kong
| | - Alexey Moskalev
- Longaevus Technologies LTD, London, United Kingdom
- Institute of biogerontology, National Research Lobachevsky State University of Nizhni Novgorod (Lobachevsky University), Nizhny Novgorod, Russia
- Gerontological Research and Clinical Center, Russian National Research Medical University, Moscow, Russia
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30
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Zheng X. An Introductory Guide to Using Bloomington Drosophila Stock Center and FlyBase for Aging Research. Cells 2024; 13:1192. [PMID: 39056774 PMCID: PMC11275189 DOI: 10.3390/cells13141192] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/02/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Studies on numerous species have demonstrated strikingly conserved mechanisms that determine the aging process, from yeasts to worms, flies, zebrafish, mice, and humans. The fruit fly Drosophila melanogaster is an excellent model organism for studying the biological basis of normal aging and etiology of age-related diseases. Since its inception in 1967, the Bloomington Drosophila Stock Center (BDSC) has grown into the largest collection of documented D. melanogaster strains (currently > 91,000). This paper aims to briefly review conserved mechanisms of aging and provides a guide to help users understand the organization of stock listings on the BDSC website and familiarize themselves with the search functions on BDSC and FlyBase, with an emphasis on using genes in conserved pathways as examples to find stocks for aging studies.
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Affiliation(s)
- Xiangzhong Zheng
- Department of Biology, Indiana University, Bloomington, IN 47401, USA
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31
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Jacquier EF, Kassis A, Marcu D, Contractor N, Hong J, Hu C, Kuehn M, Lenderink C, Rajgopal A. Phytonutrients in the promotion of healthspan: a new perspective. Front Nutr 2024; 11:1409339. [PMID: 39070259 PMCID: PMC11272662 DOI: 10.3389/fnut.2024.1409339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 06/12/2024] [Indexed: 07/30/2024] Open
Abstract
Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective-namely-how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.
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Affiliation(s)
| | | | - Diana Marcu
- School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | | | - Jina Hong
- Amway Innovation and Science, Ada, MI, United States
| | - Chun Hu
- Amway Innovation and Science, Ada, MI, United States
| | - Marissa Kuehn
- Amway Innovation and Science, Ada, MI, United States
| | | | - Arun Rajgopal
- Amway Innovation and Science, Ada, MI, United States
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32
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Chen P, Wang Y, Xie J, Lei J, Zhou B. Methylated urolithin A, mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice. Neuropharmacology 2024; 252:109950. [PMID: 38636727 DOI: 10.1016/j.neuropharm.2024.109950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 04/02/2024] [Accepted: 04/10/2024] [Indexed: 04/20/2024]
Abstract
Effective therapeutic interventions for elderly patients are lacking, despite advances in pharmacotherapy. Methylated urolithin A (mUro A), a modified ellagitannin (ET)-derived metabolite, exhibits anti-inflammatory, antioxidative, and anti-apoptotic effects. Current research has primarily investigated the neuroprotective effects of mUroA in aging mice and explored the underlying mechanisms. Our study used an in vivo aging model induced by d-galactose (D-gal) to show that mUro A notably improved learning and memory, prevented synaptic impairments by enhancing synaptic protein expression and increasing EPSCs, and reduced oxidative damage in aging mice. mUro A alleviated the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, leading to reduced glial cell activity and neuroinflammation in both accelerated aging and naturally senescent mouse models. Moreover, mUroA enhanced the activity of TCA cycle enzymes (PDH, CS, and OGDH), decreased 8-OHdG levels, and raised ATP and NAD+ levels within the mitochondria. At the molecular level, mUro A decreased phosphorylated p53 levels and increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), thus enhancing mitochondrial function. In conclusion, mUro A alleviates cognitive impairment in aging mice by suppressing neuroinflammation through NLRP3 inflammasome inhibition and restoring mitochondrial function via the p53-PGC-1α pathway. This suggests its potential therapeutic agent for brain aging and aging-related diseases.
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Affiliation(s)
- Peng Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China.
| | - Yulai Wang
- Department of Pharmacy, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, 435099, PR China
| | - Jing Xie
- Department of Pharmacy, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China
| | - Jiexin Lei
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China
| | - Benhong Zhou
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China
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33
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Peng X, Zhong Y, Mao R, He F, Cheng Y, Chen M, Zhou L, Xie H, Li J, Zhang Y. Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging. Exp Dermatol 2024; 33:e15120. [PMID: 38886965 DOI: 10.1111/exd.15120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 05/11/2024] [Accepted: 06/02/2024] [Indexed: 06/20/2024]
Abstract
Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.
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Affiliation(s)
- Xiaozhen Peng
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- School of Public Health & Laboratory Medicine, Hunan University of Medicine, Huaihua, Hunan, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Yun Zhong
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Rui Mao
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Fanping He
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Yufan Cheng
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Mengting Chen
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lei Zhou
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hongfu Xie
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ji Li
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yiya Zhang
- Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Pio-Lopez L, Levin M. Aging as a loss of morphostatic information: A developmental bioelectricity perspective. Ageing Res Rev 2024; 97:102310. [PMID: 38636560 DOI: 10.1016/j.arr.2024.102310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/21/2024] [Accepted: 04/12/2024] [Indexed: 04/20/2024]
Abstract
Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused by the accumulation of molecular and cellular damage. In this article, we propose a complementary view of aging from the perspective of endogenous bioelectricity which has not yet been integrated into aging research. We propose a view of aging as a morphostasis defect, a loss of biophysical prepattern information, encoding anatomical setpoints used for dynamic tissue and organ homeostasis. We hypothesize that this is specifically driven by abrogation of the endogenous bioelectric signaling that normally harnesses individual cell behaviors toward the creation and upkeep of complex multicellular structures in vivo. Herein, we first describe bioelectricity as the physiological software of life, and then identify and discuss the links between bioelectricity and life extension strategies and age-related diseases. We develop a bridge between aging and regeneration via bioelectric signaling that suggests a research program for healthful longevity via morphoceuticals. Finally, we discuss the broader implications of the homologies between development, aging, cancer and regeneration and how morphoceuticals can be developed for aging.
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Affiliation(s)
- Léo Pio-Lopez
- Allen Discovery Center, Tufts University, Medford, MA 02155, USA
| | - Michael Levin
- Allen Discovery Center, Tufts University, Medford, MA 02155, USA; Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
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35
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Yang C, Qu L, Wang R, Wang F, Yang Z, Xiao F. Multi-layered effects of Panax notoginseng on immune system. Pharmacol Res 2024; 204:107203. [PMID: 38719196 DOI: 10.1016/j.phrs.2024.107203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/24/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024]
Abstract
Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.
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Affiliation(s)
- Chunhao Yang
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China
| | - Liping Qu
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China; Innovation Materials Research and Development Center, Botanee Research Institute, Shanghai Jiyan Biomedical Development Co., Ltd., Shanghai 201702, China
| | - Rui Wang
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China
| | - Feifei Wang
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China; Innovation Materials Research and Development Center, Botanee Research Institute, Shanghai Jiyan Biomedical Development Co., Ltd., Shanghai 201702, China
| | - Zhaoxiang Yang
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China
| | - Fengkun Xiao
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China.
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Zhang S, Huang J, Fu J, Qin Y, Zhang X, Yao X, Zhu L, Liu H. Structurally Diverse Phenylpropanamides from Cannabis Fructus and Their Potential Neuroprotective Effects. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:12100-12118. [PMID: 38748649 DOI: 10.1021/acs.jafc.4c00242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2024]
Abstract
This study aimed to investigate the chemical components and potential health benefits of the fruits of Cannabis sativa L. Fourteen new phenylpropanamides designated as cannabisin I-XIV (1-14) and 40 known analogs were isolated and characterized via nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism. In vitro bioassay using H2O2-induced PC12 cell damage models demonstrated that hempseeds extract and compounds 1, 3, 15, 26, 30, 36, 41, and 48 exhibited neuroprotective properties. 3,3'-Demethylgrossamide (30) displayed encouraging protection activity, which was further investigated to relieve the oxidative stress and apoptosis of PC12 cells treated with H2O2. The isolation and characterization of these neuroprotective phenylpropanamides from the fruits of C. sativa provide insights into its health-promoting properties as a healthy food and herbal medicine for preventing and treating neurodegenerative diseases, especially Alzheimer's disease.
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Affiliation(s)
- Shipeng Zhang
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Jintian Huang
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Jiahui Fu
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
- Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou 310006, PR China
| | - Yu Qin
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Xue Zhang
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Xinsheng Yao
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Lingjuan Zhu
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
| | - Hongwei Liu
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China
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Zhong W, Chen J, He Y, Xiao L, Yuan C. The polysaccharides from Balanophora polyandra enhanced neuronal autophagy to ameliorate brain function decline in natural aging mice through the PI3K/AKT/mTOR signaling pathway. Neuroreport 2024; 35:509-517. [PMID: 38597274 DOI: 10.1097/wnr.0000000000002024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.
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Affiliation(s)
- Wenyan Zhong
- College of Basic Medical Sciences
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, YiChang, China
| | | | - Yumin He
- College of Basic Medical Sciences
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, YiChang, China
| | - Li Xiao
- College of Basic Medical Sciences
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, YiChang, China
| | - Chengfu Yuan
- College of Basic Medical Sciences
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, YiChang, China
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Gong L, Hou J, Yang H, Zhang X, Zhao J, Wang L, Yin X, Feng X, Yin C. Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2024; 322:117625. [PMID: 38145859 DOI: 10.1016/j.jep.2023.117625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 12/16/2023] [Accepted: 12/18/2023] [Indexed: 12/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Classical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, Asini Corii Colla, and Poria. This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. AIM OF THE STUDY To evaluate the therapeutic effect of KTC on POI and its underlying mechanism. MATERIALS AND METHODS Healthy and specific pathogen-free (SPF) female Kunming mice aged 6-8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A "drug-component-target-pathway-disease" network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting. RESULTS Compared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids, 15 terpenoids, 2 lignans, 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. CONCLUSIONS KTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.
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Affiliation(s)
- Leilei Gong
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
| | - Jinli Hou
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China.
| | - Hongjun Yang
- China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Xueyan Zhang
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
| | - Jingxia Zhao
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Lan Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Xiaojie Yin
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Xin Feng
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
| | - Chenghong Yin
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
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39
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Yang S, Sun D, Wu Y, Chen S, Guo Y, Li J, Dong G, Sheng C. Discovery of a Potent Nicotinamide Phosphoribosyltransferase Activator for Improving Aging-associated Dysfunctions. J Med Chem 2024; 67:4120-4130. [PMID: 38367219 DOI: 10.1021/acs.jmedchem.3c02370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2024]
Abstract
Nicotinamide adenine dinucleotide (NAD+) plays a crucial role in the cellular energy metabolism pathway. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in the biosynthesis of NAD+. Herein, a series of new NAMPT activators were designed to increase the NAD+ levels and improve aging-associated dysfunctions. In particular, compound C8 effectively activated NAMPT and promoted the biosynthesis of NAD+. Furthermore, we demonstrated that NAMPT activator C8 possessed excellent antiaging effects both in vitro and in vivo. Activator C8 showed potent activity in delaying aging in senescent HL-7702 cells and extended the lifespan of Caenorhabditis elegans. In a naturally aging mouse model, compound C8 effectively alleviated age-related dysfunctions and markers. Therefore, NAMPT activator C8 represented a promising lead compound for the treatment of age-related diseases.
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Affiliation(s)
- Sicheng Yang
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Donghuan Sun
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Ying Wu
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming 650032, China
| | - Shuqiang Chen
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Yuan Guo
- College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
| | - Jian Li
- School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Guoqiang Dong
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Chunquan Sheng
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
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Petr MA, Matiyevskaya F, Osborne B, Berglind M, Reves S, Zhang B, Ezra MB, Carmona-Marin LM, Syadzha MF, Mediavilla MC, Keijzers G, Bakula D, Mkrtchyan GV, Scheibye-Knudsen M. Pharmacological interventions in human aging. Ageing Res Rev 2024; 95:102213. [PMID: 38309591 DOI: 10.1016/j.arr.2024.102213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 01/15/2024] [Accepted: 01/30/2024] [Indexed: 02/05/2024]
Abstract
Pharmacological interventions are emerging as potential avenues of alleviating age-related disease. However, the knowledge of ongoing clinical trials as they relate to aging and pharmacological interventions is dispersed across a variety of mediums. In this review we summarize 136 age-related clinical trials that have been completed or are ongoing. Furthermore, we establish a database that describe the trials (AgingDB, www.agingdb.com) keeping track of the previous and ongoing clinical trials, alongside their outcomes. The aim of this review and database is to give people the ability to easily query for their trial of interest and stay up to date on the latest results. In sum, herein we give an overview of the current pharmacological strategies that have been applied to target human aging.
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Affiliation(s)
- Michael Angelo Petr
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Frida Matiyevskaya
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Brenna Osborne
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Magnus Berglind
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Simon Reves
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Bin Zhang
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Michael Ben Ezra
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Lina Maria Carmona-Marin
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Muhammad Farraz Syadzha
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Marta Cortés Mediavilla
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Guido Keijzers
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Daniela Bakula
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Garik V Mkrtchyan
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Morten Scheibye-Knudsen
- Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark.
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Zhao L, Hu K, Liu W, Qi H, Li G, Chen J, Han L. Anemonin ameliorates human diploid fibroblasts 2BS and IMR90 cell senescence by PARP1-NAD +-SIRT1 signaling pathway. Arch Gerontol Geriatr 2024; 117:105255. [PMID: 37952424 DOI: 10.1016/j.archger.2023.105255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/11/2023] [Accepted: 10/29/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE Aging becomes the most predominant risk factor for all age-associated pathological conditions with the increase of life expectancy and the aggravation of social aging. Slowing down the speed of aging is considered an effective way to improve health, but so far, effective anti-aging methods are relatively lacking. METHODS Anemonin (ANE) was screened from eight existing small-molecule compounds by cell viability assay. The function of ANE was determined by the analysis of cell proliferation, β -galactosidase (SA-β -Gal) activity, cell cycle, SASP secretion, NAD+/NADH ratio, and other aging-related indicators. The targets of ANE were predicted by Drug Target Prediction System (DTPS) and Swiss Targe Prediction System. The effect of ANE on PARP-1-NAD+-SIRT1 signaling pathway was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot, PARP1, NAD+ and SIRT1 activity detection. RESULTS ANE can delay cell senescence; PARP1 is one of the targets of ANE and plays a crucial role in ANE anti-aging; ANE release more NAD+ by inhibiting PARP1 activity, thereby conversely promoting the function of SIRT1 and delay cell senescence. CONCLUSIONS Our study indicates that ANE can delay cellular senescence through the PARP1-NAD+-SIRT1 signaling pathway, which may be considered as an effective anti-aging strategy.
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Affiliation(s)
- Lijun Zhao
- Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University Research Center on Aging, Peking University, Beijing 100191, China; Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, China
| | - Kexin Hu
- Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University Research Center on Aging, Peking University, Beijing 100191, China
| | - Weiting Liu
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, China
| | - Haonan Qi
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, China
| | - Guodong Li
- Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University Research Center on Aging, Peking University, Beijing 100191, China
| | - Jun Chen
- Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University Research Center on Aging, Peking University, Beijing 100191, China.
| | - Limin Han
- Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University Research Center on Aging, Peking University, Beijing 100191, China.
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de Magalhães JP, Abidi Z, dos Santos GA, Avelar RA, Barardo D, Chatsirisupachai K, Clark P, De-Souza EA, Johnson EJ, Lopes I, Novoa G, Senez L, Talay A, Thornton D, To P. Human Ageing Genomic Resources: updates on key databases in ageing research. Nucleic Acids Res 2024; 52:D900-D908. [PMID: 37933854 PMCID: PMC10767973 DOI: 10.1093/nar/gkad927] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 11/08/2023] Open
Abstract
Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).
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Affiliation(s)
- João Pedro de Magalhães
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
| | - Zoya Abidi
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Gabriel Arantes dos Santos
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
| | - Roberto A Avelar
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Diogo Barardo
- NOVOS Labs, 100 Park Avenue, 16th Fl, New York, NY 10017, USA
| | - Kasit Chatsirisupachai
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Peter Clark
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
| | - Evandro A De-Souza
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-970, SP, Brazil
| | - Emily J Johnson
- Computational Biology Facility, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK
| | - Inês Lopes
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Guy Novoa
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Ludovic Senez
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
| | - Angelo Talay
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
| | - Daniel Thornton
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
| | - Paul Ka Po To
- Genomics of Ageing and Rejuvenation Lab, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK
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Xu X, Xu T, Wei J, Chen T. Gut microbiota: an ideal biomarker and intervention strategy for aging. MICROBIOME RESEARCH REPORTS 2024; 3:13. [PMID: 38841415 PMCID: PMC11149087 DOI: 10.20517/mrr.2023.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 12/15/2023] [Indexed: 06/07/2024]
Abstract
Population aging is a substantial challenge for the global sanitation framework. Unhealthy aging tends to be accompanied by chronic diseases such as cardiovascular disease, diabetes, and cancer, which undermine the welfare of the elderly. Based on the fact that aging is inevitable but retarding aging is attainable, flexible aging characterization and efficient anti-aging become imperative for healthy aging. The gut microbiome, as the most dynamic component interacting with the organism, can affect the aging process through its own structure and metabolites, thus holding the potential to become both an ideal aging-related biomarker and an intervention strategy. This review summarizes the value of applying gut microbiota as aging-related microbial biomarkers in diagnosing aging state and monitoring the effect of anti-aging interventions, ultimately pointing to the future prospects of microbial intervention strategies in maintaining healthy aging.
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Affiliation(s)
- Xuan Xu
- Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China
- Huankui Academy, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China
- Authors contributed equally
| | - Tangchang Xu
- Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China
- Authors contributed equally
| | - Jing Wei
- Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China
| | - Tingtao Chen
- Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China
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Zhang Y, Wang X, Li W, Yang Y, Wu Z, Lyu Y, Yue C. Intestinal microbiota: a new perspective on delaying aging? Front Microbiol 2023; 14:1268142. [PMID: 38098677 PMCID: PMC10720643 DOI: 10.3389/fmicb.2023.1268142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/17/2023] [Indexed: 12/17/2023] Open
Abstract
The global aging situation is severe, and the medical pressures associated with aging issues should not be underestimated. The need and feasibility of studying aging and intervening in aging have been confirmed. Aging is a complex natural physiological progression, which involves the irreversible deterioration of body cells, tissues, and organs with age, leading to enhanced risk of disease and ultimately death. The intestinal microbiota has a significant role in sustaining host dynamic balance, and the study of bidirectional communication networks such as the brain-gut axis provides important directions for human disease research. Moreover, the intestinal microbiota is intimately linked to aging. This review describes the intestinal microbiota changes in human aging and analyzes the causal controversy between gut microbiota changes and aging, which are believed to be mutually causal, mutually reinforcing, and inextricably linked. Finally, from an anti-aging perspective, this study summarizes how to achieve delayed aging by targeting the intestinal microbiota. Accordingly, the study aims to provide guidance for further research on the intestinal microbiota and aging.
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Affiliation(s)
- Yuemeng Zhang
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
| | - Xiaomei Wang
- Yan’an University of Physical Education, Yan’an University, Yan’an, Shaanxi, China
| | - Wujuan Li
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
| | - Yi Yang
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
| | - Zhuoxuan Wu
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
| | - Yuhong Lyu
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
| | - Changwu Yue
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, China
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Moskalev AA. Potential Geroprotectors - From Bench to Clinic. BIOCHEMISTRY. BIOKHIMIIA 2023; 88:1732-1738. [PMID: 38105194 DOI: 10.1134/s0006297923110056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 09/20/2023] [Accepted: 09/20/2023] [Indexed: 12/19/2023]
Abstract
Geroprotectors are substances that slow down aging process and can be used for prevention of age-related diseases. Geroprotectors can improve functioning of various organ systems and enhance their homeostatic capabilities. We have developed a system of criteria for geroprotectors and proposed their classification based on the mechanisms of their action on the aging processes. Geroprotectors are required to reduce mortality, improve human aging biomarkers, have minimal side effects, and enhance quality of life. Additionally, there are approaches based on combining geroprotectors targeted to different targets and mechanisms of aging to achieve maximum effectiveness. Currently, numerous preclinical studies are being conducted to identify new molecular targets and develop new approaches to extend healthy aging, although the number of clinical trials is limited. Geroprotectors have the potential to become a new class of preventive medicines as they prevent onset of certain diseases or slow down their progression.
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Affiliation(s)
- Alexey A Moskalev
- Institute of Biogerontology, Lobachevsky University, Nizhny Novgorod, 603950, Russia.
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46
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Venn-Watson S, Schork NJ. Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds. Nutrients 2023; 15:4607. [PMID: 37960259 PMCID: PMC10649853 DOI: 10.3390/nu15214607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 11/15/2023] Open
Abstract
Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.
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Affiliation(s)
- Stephanie Venn-Watson
- Epitracker Inc., San Diego, CA 92106, USA
- Seraphina Therapeutics, Inc., San Diego, CA 92106, USA;
| | - Nicholas J. Schork
- Seraphina Therapeutics, Inc., San Diego, CA 92106, USA;
- Translational Genomics Research Institute (TGen), City of Hope, Phoenix, AZ 85004, USA
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47
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Parkhitko AA, Filine E, Tatar M. Combinatorial interventions in aging. NATURE AGING 2023; 3:1187-1200. [PMID: 37783817 PMCID: PMC11194689 DOI: 10.1038/s43587-023-00489-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 08/15/2023] [Indexed: 10/04/2023]
Abstract
Insight on the underlying mechanisms of aging will advance our ability to extend healthspan, treat age-related pathology and improve quality of life. Multiple genetic and pharmacological manipulations extend longevity in different species, yet monotherapy may be relatively inefficient, and we have limited data on the effect of combined interventions. Here we summarize interactions between age-related pathways and discuss strategies to simultaneously retard these in different organisms. In some cases, combined manipulations additively increase their impact on common hallmarks of aging and lifespan, suggesting they quantitatively participate within the same pathway. In other cases, interactions affect different hallmarks, suggesting their joint manipulation may independently maximize their effects on lifespan and healthy aging. While most interaction studies have been conducted with invertebrates and show varying levels of translatability, the conservation of pro-longevity pathways offers an opportunity to identify 'druggable' targets relevant to multiple human age-associated pathologies.
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Affiliation(s)
- Andrey A Parkhitko
- Aging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
| | - Elizabeth Filine
- Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
| | - Marc Tatar
- Department of Ecology, Evolution and Organismal Biology, Brown University, Providence, RI, USA.
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Miller SJ, Darji RY, Walaieh S, Lewis JA, Logan R. Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson's disease. Front Neurol 2023; 14:1271941. [PMID: 37840914 PMCID: PMC10568035 DOI: 10.3389/fneur.2023.1271941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/04/2023] [Indexed: 10/17/2023] Open
Abstract
Drosophila melanogaster is a valuable model organism for a wide range of biological exploration. The well-known advantages of D. melanogaster include its relatively simple biology, the ease with which it is genetically modified, the relatively low financial and time costs associated with their short gestation and life cycles, and the large number of offspring they produce per generation. D. melanogaster has facilitated the discovery of many significant insights into the pathology of Parkinson's disease (PD) and has served as an excellent preclinical model of PD-related therapeutic discovery. In this review, we provide an overview of the major D. melanogaster models of PD, each of which provide unique insights into PD-relevant pathology and therapeutic targets. These models are discussed in the context of their past, current, and future potential use for studying the utility of secondary metabolites as therapeutic agents in PD. Over the last decade, senolytics have garnered an exponential interest in their ability to mitigate a broad spectrum of diseases, including PD. Therefore, an emphasis is placed on the senolytic and senomorphic properties of secondary metabolites. It is expected that D. melanogaster will continue to be critical in the effort to understand and improve treatment of PD, including their involvement in translational studies focused on secondary metabolites.
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Affiliation(s)
- Sean J. Miller
- Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, United States
| | - Rayyan Y. Darji
- Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, United States
| | - Sami Walaieh
- Department of Biology, Eastern Nazarene College, Quincy, MA, United States
| | - Jhemerial A. Lewis
- Department of Biology, Eastern Nazarene College, Quincy, MA, United States
| | - Robert Logan
- Department of Biology, Eastern Nazarene College, Quincy, MA, United States
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Lee HS, Choi CI. Black Goji Berry ( Lycium ruthenicum Murray): A Review of Its Pharmacological Activity. Nutrients 2023; 15:4181. [PMID: 37836464 PMCID: PMC10574788 DOI: 10.3390/nu15194181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
Lycium ruthenicum Murray (LRM; commonly known as black goji berry or black wolfberry), a plant in the Solanaceae family, grows in the deserts of China's Qinghai-Tibet plateau. LRM is widely consumed in traditional Chinese medicine, and its fruits are frequently used as herbal remedies to treat heart disease, fatigue, inflammation, and other conditions. Many studies have reported that LRM is rich in functional phytochemicals, such as anthocyanins and polysaccharides, and has various pharmacological actions. This article reviews research on the biological and pharmacological effects of the constituents of LRM fruits. LRM has various pharmacological properties, such as antioxidant, anti-inflammatory, anti-radiation, immune-enhancing, anti-tumor, and protective effects. LRM has much promise as a dietary supplement for preventing many types of chronic metabolic disease.
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Affiliation(s)
| | - Chang-Ik Choi
- Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea;
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50
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Uemura T, Matsunaga M, Yokota Y, Takao K, Furuchi T. Inhibition of Polyamine Catabolism Reduces Cellular Senescence. Int J Mol Sci 2023; 24:13397. [PMID: 37686212 PMCID: PMC10488189 DOI: 10.3390/ijms241713397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/25/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine, spermidine, and spermine) are essential for cell growth and function. Age-related reductions in polyamine levels have been shown to be associated with reduced cognitive and physical functions. We have previously found that the expression of spermine oxidase (SMOX) increases with age; however, the relationship between SMOX expression and cellular senescence remains unclear. Therefore, we investigated the relationship between increased SMOX expression and cellular senescence using human-liver-derived HepG2 cells. Intracellular spermine levels decreased and spermidine levels increased with the serial passaging of cells (aged cells), and aged cells showed increased expression of SMOX. The levels of acrolein-conjugated protein, which is produced during spermine degradation, also increases. Senescence-associated β-gal activity was increased in aged cells, and the increase was suppressed by MDL72527, an inhibitor of acetylpolyamine oxidase (AcPAO) and SMOX, both of which are enzymes that catalyze polyamine degradation. DNA damage accumulated in aged cells and MDL72527 reduced DNA damage. These results suggest that the SMOX-mediated degradation of spermine plays an important role in cellular senescence. Our results demonstrate that cellular senescence can be controlled by inhibiting spermine degradation using a polyamine-catabolizing enzyme inhibitor.
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Affiliation(s)
- Takeshi Uemura
- Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, Japan (K.T.); (T.F.)
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