1
|
López-Castañón N, Casquero S, Villanueva-Santos V, Pérez-Rodríguez L, Romero-Haro AÁ. The Impairment of Body Condition Transiently Increases Oxidative Stress: A Dietary Restriction Experiment in Partridges. JOURNAL OF EXPERIMENTAL ZOOLOGY. PART A, ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY 2025. [PMID: 40391460 DOI: 10.1002/jez.2930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 04/29/2025] [Accepted: 05/09/2025] [Indexed: 05/21/2025]
Abstract
A proper body condition determines the correct functioning of physiological processes and the optimal expression of fitness-related traits. Among these processes, maintaining the redox balance is essential to protect the organism from damage caused by oxidative stress. Yet, the causal link between an impaired body condition and a consequent increase in oxidative stress remains surprisingly far from clear. We experimentally tested such link by imposing a dietary restriction (DR), that is, decreased food availability, to nonreproductive adult red-legged partridges (Alectoris rufa) and measuring a battery of oxidative stress biomarkers. Levels of oxidative status (ratio of reduced to oxidized glutathione [GSH:GSSG] in erythrocytes), oxidative damage in plasma lipids (MDA), and plasma antioxidant capacity (OXY and TEAC assays) were quantified before the DR, twice during the DR, and once after the end of the DR. The GSH:GSSG ratio remained steady throughout the experiment. By contrast, after 19 days under DR, individuals showed an increase in MDA levels and an altered antioxidant capacity (a reduction in OXY and an increase in TEAC) with respect to controls, showing that the worsening of body condition indeed leads to an increase of the oxidative stress. However, these effects were transitory, appearing only by 19 days under DR and disappearing afterwards. These findings suggest that, despite the temporary increase in oxidative damage, individuals adapt their oxidative physiology to overcome resource restriction, possibly by reallocating resources from other physiological processes. This highlights the importance of considering dynamic changes when evaluating the impact of stressful conditions.
Collapse
Affiliation(s)
- Nerea López-Castañón
- Instituto de Investigación en Recursos Cinegéticos (IREC), CSIC-UCLM-JCCM, Ciudad Real, Spain
| | - Silvia Casquero
- Instituto de Investigación en Recursos Cinegéticos (IREC), CSIC-UCLM-JCCM, Ciudad Real, Spain
| | | | - Lorenzo Pérez-Rodríguez
- Instituto de Investigación en Recursos Cinegéticos (IREC), CSIC-UCLM-JCCM, Ciudad Real, Spain
| | - Ana Ángela Romero-Haro
- Instituto de Investigación en Recursos Cinegéticos (IREC), CSIC-UCLM-JCCM, Ciudad Real, Spain
- Department of Evolutionary Ecology, National Museum of Natural Sciences (MNCN-CSIC), Madrid, Spain
| |
Collapse
|
2
|
Biancani B, Carosi M, Capasso M, Rossi G, Tafuri S, Ciani F, Cotignoli C, Zinno F, Venturelli E, Galliani M, Spani F. Assessment of Oxidative Stress and Biometric Data in a Captive Colony of Hamadryas Baboons ( Papio hamadryas Linnaeus, 1758) at the Ravenna Zoo Safari (Italy). Vet Sci 2025; 12:466. [PMID: 40431559 PMCID: PMC12115884 DOI: 10.3390/vetsci12050466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2025] [Revised: 05/09/2025] [Accepted: 05/10/2025] [Indexed: 05/29/2025] Open
Abstract
This study evaluates the health of a captive colony of Hamadryas baboons at Ravenna Zoo Safari (Italy), focusing on oxidative stress markers and biometric data. Forty-eight individuals were assessed during routine veterinary procedures: males underwent vasectomy, and females were checked for pregnancy. Biometric data collected included body weight, body length, and genital measurements in males, while females were evaluated for reproductive status. Oxidative stress was measured using two tests that assess both harmful pro-oxidant levels and the body's antioxidant defenses. Results showed no significant differences in oxidative stress levels between sexes, although males and females differed in body weight. Pregnant and postpartum females exhibited higher oxidative stress, likely due to the metabolic and hormonal demands of reproduction. This supports the idea that reproductive activity increases the production of reactive oxygen species, requiring stronger antioxidant responses. In males, correlations between body weight and genital measurements suggest these could help estimate age in the absence of birth records. No link was found between oxidative stress and body weight, indicating limited age-related effects on these markers. Overall, the study highlights the importance of monitoring oxidative stress in captive primates to better understand the effects of reproduction and aging, and to improve welfare and management practices.
Collapse
Affiliation(s)
- Barbara Biancani
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy; (M.C.); (S.T.); (F.C.); (F.Z.)
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy;
| | - Monica Carosi
- Department of Science, Roma Tre University, 00146 Rome, Italy;
| | - Michele Capasso
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy; (M.C.); (S.T.); (F.C.); (F.Z.)
| | - Giacomo Rossi
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy;
| | - Simona Tafuri
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy; (M.C.); (S.T.); (F.C.); (F.Z.)
| | - Francesca Ciani
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy; (M.C.); (S.T.); (F.C.); (F.Z.)
| | - Chiara Cotignoli
- Zoo Safari Ravenna, 48125 Ravenna, Italy; (C.C.); (E.V.); (M.G.)
| | - Francesco Zinno
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy; (M.C.); (S.T.); (F.C.); (F.Z.)
| | - Elena Venturelli
- Zoo Safari Ravenna, 48125 Ravenna, Italy; (C.C.); (E.V.); (M.G.)
| | - Matteo Galliani
- Zoo Safari Ravenna, 48125 Ravenna, Italy; (C.C.); (E.V.); (M.G.)
| | - Federica Spani
- Department of Science and Technology for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy;
| |
Collapse
|
3
|
Machado IF, Palmeira CM, Rolo AP. Sestrin2 is a central regulator of mitochondrial stress responses in disease and aging. Ageing Res Rev 2025; 109:102762. [PMID: 40320152 DOI: 10.1016/j.arr.2025.102762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 04/09/2025] [Accepted: 04/30/2025] [Indexed: 05/08/2025]
Abstract
Mitochondria supply most of the energy for cellular functions and coordinate numerous cellular pathways. Their dynamic nature allows them to adjust to stress and cellular metabolic demands, thus ensuring the preservation of cellular homeostasis. Loss of normal mitochondrial function compromises cell survival and has been implicated in the development of many diseases and in aging. Although exposure to continuous or severe stress has adverse effects on cells, mild mitochondrial stress enhances mitochondrial function and potentially extends health span through mitochondrial adaptive responses. Over the past few decades, sestrin2 (SESN2) has emerged as a pivotal regulator of stress responses. For instance, SESN2 responds to genotoxic, oxidative, and metabolic stress, promoting cellular defense against stress-associated damage. Here, we focus on recent findings that establish SESN2 as an orchestrator of mitochondrial stress adaptation, which is supported by its involvement in the integrated stress response, mitochondrial biogenesis, and mitophagy. Additionally, we discuss the integral role of SESN2 in mediating the health benefits of exercise as well as its impact on skeletal muscle, liver and heart injury, and aging.
Collapse
Affiliation(s)
- Ivo F Machado
- CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CiBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute of Interdisciplinary Research, Doctoral Program in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, Coimbra, Portugal
| | - Carlos M Palmeira
- CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CiBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal
| | - Anabela P Rolo
- CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CiBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
| |
Collapse
|
4
|
Ohishi K, Rahman AA, Ohkura T, Burns AJ, Goldstein AM, Hotta R. Effects of aged garlic extract on aging?related changes in gastrointestinal function and enteric nervous system cells. Exp Ther Med 2025; 29:103. [PMID: 40171138 PMCID: PMC11959352 DOI: 10.3892/etm.2025.12853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 02/05/2025] [Indexed: 04/03/2025] Open
Abstract
Dysmotility of the gastrointestinal (GI) tract is commonly seen in elderly individuals, where it causes significant morbidity and can lead to more severe conditions, including sarcopenia and frailty. Although the precise mechanisms underlying aging-related GI dysmotility are not fully understood, neuronal loss or degeneration in the enteric nervous system (ENS) may be involved. Aged garlic extract (AGE) has been shown to have several beneficial effects in the GI tract; however, it is not known whether AGE can improve GI motility in older animals. The aim of the present study was to examine the effects of AGE on the ENS and gut motility in older mice and elucidate potential mechanisms of action. An AGE-formulated diet was given to 18-month-old female mice for 2 weeks. Organ bath studies and cell culture demonstrated that AGE: i) Altered gut contractile activity; ii) enhanced viability of ENS cells; and iii) exhibited neuroprotective effects on the ENS via reduction in oxidative stress. These findings suggest that AGE could be used to develop novel dietary therapeutics for aging-related GI dysmotility by targeting the associated loss and damage of the ENS.
Collapse
Affiliation(s)
- Kensuke Ohishi
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima 739-1195, Japan
| | - Ahmed A. Rahman
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Takahiro Ohkura
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Alan J. Burns
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Allan M. Goldstein
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Ryo Hotta
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| |
Collapse
|
5
|
Tavasoli A, Okwuegbuna OK, Tang B, Iudicello JE, Kallianpur AR, Ellis RJ, Letendre SL. Hepcidin modifies the relationship between anemia, erythrocyte indices, and neurocognitive performance in virally suppressed people with HIV. AIDS 2025; 39:658-666. [PMID: 39764772 PMCID: PMC12077814 DOI: 10.1097/qad.0000000000004110] [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: 11/04/2024] [Accepted: 12/23/2024] [Indexed: 04/04/2025]
Abstract
OBJECTIVE Neurocognitive impairment in people with HIV (PWH) is associated with erythrocyte indices, which may serve as indicators of iron metabolism, inflammation, and related factors. Erythropoiesis requires iron, regulated by a multifaceted system of peptide hormones, including hepcidin. This study postulated that hepcidin might modify the relationship between erythrocyte indices and neurocognitive performance in PWH. METHODS Plasma hepcidin and erythrocyte indices were quantified in 88 virally suppressed PWH who underwent comprehensive neurocognitive assessments. Global neurocognitive performance was summarized by global T -scores. Associations of global T -scores with anemia and erythrocyte indices were determined in univariable analyses. To examine the influence of hepcidin on the relationship between neurocognitive performance and erythrocyte indices, we evaluated interactions between these covariates in relation to global T -scores and then performed stratified analyses. RESULTS In multivariable analyses, hepcidin detectability interacted with age ( P = 0.007) and mean corpuscular volume (MCV; P = 0.031) in relation to the global T -score. Interactions between anemia and erythrocyte indices on global T -scores were significant (anemia × MCV, P = 0.008; anemia × MCH, P = 0.011). Stratified analyses identified that lower global T -scores were associated with older age ( P = 0.001) and higher MCV ( P = 0.0046) and mean corpuscular hemoglobin (MCH, P = 0.026) only when hepcidin was undetectable. Among the anemic, worse global T -score was associated with higher MCV ( P = 0.001) and MCH ( P = 0.002). CONCLUSION Findings suggest that iron-related factors (hepcidin, anemia, MCV, MCH) and age influence neurocognitive health. This cross-sectional study underscores hepcidin as an effect modifier in the associations of erythrocyte indices, anemia, and age with neurocognitive function in PWH.
Collapse
Affiliation(s)
- Azin Tavasoli
- Department of Neurosciences, University of California San Diego, San Diego, CA, USA
| | | | - Bin Tang
- Department of Psychiatry, University of California San Diego, San Diego, CA, USA
| | | | - Asha R. Kallianpur
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Ronald J. Ellis
- Department of Neurosciences, University of California San Diego, San Diego, CA, USA
| | - Scott L. Letendre
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| |
Collapse
|
6
|
Faraguna S, Milinković Tur S, Sobočanec S, Pinterić M, Belić M. Assessment of Oxidative Stress and Associated Biomarkers in Wild Avian Species. Animals (Basel) 2025; 15:1203. [PMID: 40362019 PMCID: PMC12071163 DOI: 10.3390/ani15091203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 05/15/2025] Open
Abstract
Reactive oxygen species (ROS) are natural by-products of cellular metabolism and are also formed in response to environmental stressors such as pollution, extreme temperatures, and ultraviolet radiation exposure. Physiological factors such as intense activity, growth, reproduction, nutrient deficiency, captivity, and disease also contribute to ROS production. While ROS, including free radicals, play a key role in cell physiology, including immune defense, their excessive accumulation can damage cellular components and cause oxidative stress when antioxidant defenses are overwhelmed. To regulate ROS levels, wild birds rely on enzymatic (e.g., catalase, superoxide dismutase, glutathione peroxidase) and non-enzymatic antioxidants (e.g., vitamins C and E, carotenoids). Oxidative stress affects important aspects of wild bird biology, including health, reproduction, and survival, and is closely linked to overall fitness. It is also linked to physiological challenges such as migration and the progression of various diseases affecting wild bird populations. The study of oxidative stress in wild birds requires the use of appropriate biomarkers to assess its role in disease development. A deeper understanding of the balance between ROS production and antioxidant defenses is essential to determine how wild birds cope with environmental and physiological challenges. In this review, we summarize the mechanisms of oxidative stress in wild birds and the role of antioxidants in maintaining health and promoting longevity in wild bird populations.
Collapse
Affiliation(s)
- Siniša Faraguna
- Department of Pathophysiology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Suzana Milinković Tur
- Department of Physiology and Radiobiology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Sandra Sobočanec
- Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (S.S.); (M.P.)
| | - Marija Pinterić
- Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (S.S.); (M.P.)
| | - Maja Belić
- Department of Pathophysiology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| |
Collapse
|
7
|
Davis E, Ermi AG, Sarkar D. Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH): A Promising Molecular Marker and Therapeutic Target for Hepatocellular Carcinoma. Cancers (Basel) 2025; 17:1375. [PMID: 40282551 PMCID: PMC12025727 DOI: 10.3390/cancers17081375] [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: 03/10/2025] [Revised: 04/16/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to have an influential role in HCC progression and the development of an aggressive phenotype. AEG-1 has been shown to be upregulated in many cancers, including HCC. Studies have shown that it plays a crucial role in the proliferation, invasion and metastasis, and evasion of apoptosis in HCC. Its relationship with proteins and pathways, such as MYC, SND1, PI3K/AKT, and other signaling pathways demonstrates its pertinent role in oncogenic development and relevance as a biomarker and therapeutic target. Recent studies have shown that AEG-1 is present in tumor tissues, and the anti-AEG-1 antibody is detected in the blood of cancer patients, demonstrating its viability as a diagnostic/prognostic marker. This review paper shines light on recent findings regarding the molecular implications of AEG-1, with emphasis on its role of regulating metabolic dysfunction-associated steatohepatitis (MASH), a key predisposing factor for HCC, new treatment strategies targeting AEG-1, and challenges associated with analyzing this intriguing molecule.
Collapse
Affiliation(s)
- Eva Davis
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Ali Gawi Ermi
- Department of Cellular, Molecular and Genetic Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Devanand Sarkar
- Department of Cellular, Molecular and Genetic Medicine, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
| |
Collapse
|
8
|
Manickam R, Santhana S, Xuan W, Bisht KS, Tipparaju SM. Nampt: a new therapeutic target for modulating NAD + levels in metabolic, cardiovascular, and neurodegenerative diseases. Can J Physiol Pharmacol 2025. [PMID: 40203459 DOI: 10.1139/cjpp-2024-0400] [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: 04/11/2025]
Abstract
NAD+ is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD+/NADH ratio is linked to many diseases. NAD+ is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD+ is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD+ is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD+/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD+ is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD+ in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD+ restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD+ axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.
Collapse
Affiliation(s)
- Ravikumar Manickam
- Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Sandhya Santhana
- Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Wanling Xuan
- Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Kirpal S Bisht
- Department of Chemistry, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, USA
| | - Srinivas M Tipparaju
- Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| |
Collapse
|
9
|
Zhang Y, Tan S, Kim JH, Cao J, Zhao Y, Pang Z, Liu J, Lv Y, Ding F, Kim J, Woo HR, Xia X, Guo H, Li Z. The kinase ATM delays Arabidopsis leaf senescence by stabilizing the phosphatase MKP2 in a phosphorylation-dependent manner. THE PLANT CELL 2025; 37:koaf066. [PMID: 40132114 PMCID: PMC11979455 DOI: 10.1093/plcell/koaf066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 02/23/2025] [Indexed: 03/27/2025]
Abstract
Arabidopsis thaliana (Arabidopsis) Ataxia Telangiectasia Mutated (ATM) kinase plays a vital role in orchestrating leaf senescence; however, the precise mechanisms remain elusive. Here, our study demonstrates that ATM kinase activity is essential for mitigating age- and reactive oxygen species-induced senescence, as restoration of wild-type ATM reverses premature senescence in the atm mutant, while a kinase-dead ATM variant is ineffective. ATM physically interacts with and phosphorylates Mitogen-Activated Protein Kinase Phosphatase 2 (MKP2) to enhance stability under oxidative stress. Mutations in putative phosphorylation sites S15/154 on MKP2 disrupt its phosphorylation, stability, and senescence-delaying function. Moreover, mutation of mitogen-activated protein kinase 6, a downstream target of MKP2, alleviates the premature senescence phenotype of the atm mutant. Notably, the dual-specificity protein phosphatase 19 (HsDUSP19), a predicted human counter protein of MPK2, interacts with both ATM and HsATM and extends leaf longevity in Arabidopsis when overexpressed. These findings elucidate the molecular mechanisms underlying the role of ATM in leaf senescence and suggest that the ATM-MKP2 module is likely evolutionarily conserved in regulating the aging process across eukaryotes.
Collapse
Affiliation(s)
- Yi Zhang
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Shuya Tan
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Jin Hee Kim
- Subtropical Horticulture Research Institute, Jeju National University, Jeju 63243, Republic of Korea
| | - Jie Cao
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Yaning Zhao
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Zhenpei Pang
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Junjie Liu
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Yonglun Lv
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Feng Ding
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Jeongsik Kim
- Faculty of Science Education and Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Republic of Korea
| | - Hye Ryun Woo
- Department of New Biology, DGIST, Daegu 42988, Republic of Korea
| | - Xinli Xia
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| | - Hongwei Guo
- Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China
| | - Zhonghai Li
- State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
| |
Collapse
|
10
|
Duan RC, Zhang YN, Wang YH, Xie BX, Du ZZ, Chen FJ. NPF and sNPF can regulate the feeding behaviour and affect the growth and antioxidant levels of the rice brown planthopper, Nilaparvata lugens. INSECT MOLECULAR BIOLOGY 2025; 34:302-310. [PMID: 39497249 DOI: 10.1111/imb.12971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/21/2024] [Indexed: 03/05/2025]
Abstract
Neuropeptide F (NPF) and short neuropeptide F (sNPF) are important neuropeptides and mainly affect feeding behaviour of insects. However, the regulation of insect feeding behaviour by NPF and sNPF appears to differ between species, and it is not clear how NPF and sNPF regulate the food intake of the brown planthopper (Nilaparvata lugens). Therefore, the functions of NPF and sNPF in regulating food intake and affecting the growth and antioxidant levels of N. lugens fed on host rice plants were investigated by knocking down NPF and sNPF respectively and simultaneously knocking down both of them by RNA interference. The results showed that NPF and sNPF were mainly expressed in the head of N. lugens, and N. lugens increased food intake after NPF and sNPF were knocked down, which was reflected in the prolonged duration of N4a and N4b waves in the electrical penetration graph (EPG) experiment after knocking down NPF and sNPF. In addition, knocking down NPF and sNPF led to the increase of body weight and mortality of N. lugens, and also led to the increase of antioxidant level of N. lugens. So it was concluded that NPF and sNPF could regulate food intake, maintain body weight stability and oxidative balance in N. lugens. Our study clarified the molecular mechanism of NPF and sNPF regulating feeding behaviour and affect the growth and antioxidant level of N. lugens.
Collapse
Affiliation(s)
- Rui-Chuan Duan
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Yu-Ning Zhang
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Yan-Hui Wang
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Bo-Xuan Xie
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Zheng-Ze Du
- College of Life Science, Nanjing Agricultural University, Nanjing, China
| | - Fa-Jun Chen
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| |
Collapse
|
11
|
Guzman SD, Brooks SV. Skeletal muscle innervation: Reactive oxygen species as regulators of neuromuscular junction dynamics and motor unit remodeling. Free Radic Biol Med 2025; 230:58-65. [PMID: 39892501 PMCID: PMC11893230 DOI: 10.1016/j.freeradbiomed.2025.01.053] [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: 09/17/2024] [Revised: 01/21/2025] [Accepted: 01/29/2025] [Indexed: 02/03/2025]
Abstract
This review explores the intricate processes of motor unit remodeling with a specific focus on the influence of reactive oxygen species (ROS) and oxidative stress on the primary cellular components: nerves/axons, muscle fibers, and muscle-resident glial cells. Emphasizing the role of redox biology, we highlight how oxidative stress impacts motor unit adaptation, injury response, and aging. By synthesizing findings from recent studies with seminal works, including investigations of myelin and terminal Schwann cells and neuromuscular junction (NMJ) dynamics, this review provides a comprehensive understanding of the molecular mechanisms underpinning motor unit maintenance and repair. The goal is to elucidate how oxidative stress influences these processes and to explore potential therapeutic strategies for neuromuscular disorders.
Collapse
Affiliation(s)
- Steve D Guzman
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Susan V Brooks
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
| |
Collapse
|
12
|
Olatunji M, Liu Y. RNA damage and its implications in genome stability. DNA Repair (Amst) 2025; 147:103821. [PMID: 40043352 DOI: 10.1016/j.dnarep.2025.103821] [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: 11/26/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 03/17/2025]
Abstract
Endogenous and environmental stressors can damage DNA and RNA to compromise genome and transcriptome stability and integrity in cells, leading to genetic instability and diseases. Recent studies have demonstrated that RNA damage can also modulate genome stability via RNA-templated DNA synthesis, suggesting that it is essential to maintain RNA integrity for the sustainment of genome stability. However, little is known about RNA damage and repair and their roles in modulating genome stability. Current efforts have mainly focused on revealing RNA surveillance pathways that detect and degrade damaged RNA, while the critical role of RNA repair is often overlooked. Due to their abundance and susceptibility to nucleobase damaging agents, it is essential for cells to evolve robust RNA repair mechanisms that can remove RNA damage, maintaining RNA integrity during gene transcription. This is supported by the discovery of the alkylated RNA nucleobase repair enzyme human AlkB homolog 3 that can directly remove the methyl group on damaged RNA nucleobases, predominantly in the nucleus of human cells, thereby restoring the integrity of the damaged RNA nucleobases. This is further supported by the fact that several DNA repair enzymes can also process RNA damage. In this review, we discuss RNA damage and its effects on cellular function, DNA repair, genome instability, and potential RNA damage repair mechanisms. Our review underscores the necessity for future research on RNA damage and repair and their essential roles in modulating genome stability.
Collapse
Affiliation(s)
- Mustapha Olatunji
- Biochemistry Ph.D. Program, Florida International University, Miami, FL, USA
| | - Yuan Liu
- Biochemistry Ph.D. Program, Florida International University, Miami, FL, USA; Department of Chemistry and Biochemistry, and Florida International University, Miami, FL, USA; Biomolecular Sciences Institute, Florida International University, Miami, FL, USA.
| |
Collapse
|
13
|
Lee J, Roh JL. Ferroptosis: iron release mechanisms in the bioenergetic process. Cancer Metastasis Rev 2025; 44:36. [PMID: 40000477 DOI: 10.1007/s10555-025-10252-8] [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: 11/15/2024] [Accepted: 02/17/2025] [Indexed: 02/27/2025]
Abstract
Ferroptosis, an iron-dependent form of cell death, has been the focus of extensive research over the past decade, leading to the elucidation of key molecules and mechanisms involved in this process. While several studies have highlighted iron sources for the Fenton reaction, the predominant mechanism for iron release in ferroptosis has been identified as ferritinophagy, which occurs in response to iron starvation. However, much of the existing literature has concentrated on lipid peroxidation rather than on the mechanisms of iron release. This review proposes three distinct mechanisms of iron mobilization: ferritinophagy, reductive pathways with selective gating of ferritin pores, and quinone-mediated iron mobilization. Notably, the latter two mechanisms operate independently of iron starvation and rely primarily on reductants such as NADH and O2•-. The inhibition of the respiratory chain, particularly under the activation of α-ketoglutarate dehydrogenase, leads to the accumulation of these reductants, which in turn promotes iron release from ferritin and indirectly inhibits AMP-activated protein kinase through excessive iron levels. In this work, we delineate the intricate relationship between iron mobilization and bioenergetic processes under conditions of oxidative stress. Furthermore, this review aims to enhance the understanding of the connections between ferroptosis and these mechanisms.
Collapse
Affiliation(s)
- Jaewang Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-Do, 13496, Republic of Korea
- Department of Biomedical Science, General Graduate School, CHA University, Pocheon, Republic of Korea
| | - Jong-Lyel Roh
- Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-Do, 13496, Republic of Korea.
- Department of Biomedical Science, General Graduate School, CHA University, Pocheon, Republic of Korea.
| |
Collapse
|
14
|
Biga PR, Duan JE, Young TE, Marks JR, Bronikowski A, Decena LP, Randolph EC, Pavuluri AG, Li G, Fang Y, Wilkinson GS, Singh G, Nigrin NT, Larschan EN, Lonski AJ, Riddle NC. Hallmarks of aging: A user's guide for comparative biologists. Ageing Res Rev 2025; 104:102616. [PMID: 39643212 DOI: 10.1016/j.arr.2024.102616] [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: 05/30/2024] [Revised: 11/25/2024] [Accepted: 12/02/2024] [Indexed: 12/09/2024]
Abstract
Since the first description of a set of characteristics of aging as so-called hallmarks or pillars in 2013/2014, these characteristics have served as guideposts for the research in aging biology. They have been examined in a range of contexts, across tissues, in response to disease conditions or environmental factors, and served as a benchmark for various anti-aging interventions. While the hallmarks of aging were intended to capture generalizable characteristics of aging, they are derived mostly from studies of rodents and humans. Comparative studies of aging including species from across the animal tree of life have great promise to reveal new insights into the mechanistic foundations of aging, as there is a great diversity in lifespan and age-associated physiological changes. However, it is unclear how well the defined hallmarks of aging apply across diverse species. Here, we review each of the twelve hallmarks of aging defined by Lopez-Otin in 2023 with respect to the availability of data from diverse species. We evaluate the current methods used to assess these hallmarks for their potential to be adapted for comparative studies. Not unexpectedly, we find that the data supporting the described hallmarks of aging are restricted mostly to humans and a few model systems and that no data are available for many animal clades. Similarly, not all hallmarks can be easily assessed in diverse species. However, for at least half of the hallmarks, there are methods available today that can be employed to fill this gap in knowledge, suggesting that these studies can be prioritized while methods are developed for comparative study of the remaining hallmarks.
Collapse
Affiliation(s)
- Peggy R Biga
- Department of Biology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jingyue E Duan
- Department of Animal Science, Cornell University, Ithaca, NY, USA
| | - Tristan E Young
- Department of Biology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jamie R Marks
- Department of Integrative Biology, W. K. Kellogg Biological Station, Michigan State University, Hickory Corners, MI, USA
| | - Anne Bronikowski
- Department of Integrative Biology, W. K. Kellogg Biological Station, Michigan State University, Hickory Corners, MI, USA
| | - Louis P Decena
- Department of Integrative Biology, W. K. Kellogg Biological Station, Michigan State University, Hickory Corners, MI, USA
| | - Eric C Randolph
- Department of Biology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ananya G Pavuluri
- Center for Computational Molecular Biology, Brown University, Providence, RI, USA
| | - Guangsheng Li
- Department of Animal Science, Cornell University, Ithaca, NY, USA
| | - Yifei Fang
- Department of Animal Science, Cornell University, Ithaca, NY, USA
| | | | - Gunjan Singh
- Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, USA
| | - Nathan T Nigrin
- Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, USA
| | - Erica N Larschan
- Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, USA
| | - Andrew J Lonski
- Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, RI, USA
| | - Nicole C Riddle
- Department of Biology, The University of Alabama at Birmingham, Birmingham, AL, USA.
| |
Collapse
|
15
|
Yang Y, Wu Y, Xiang L, Picardo M, Zhang C. Deciphering the role of skin aging in pigmentary disorders. Free Radic Biol Med 2025; 227:638-655. [PMID: 39674424 DOI: 10.1016/j.freeradbiomed.2024.12.032] [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: 05/30/2024] [Revised: 12/08/2024] [Accepted: 12/11/2024] [Indexed: 12/16/2024]
Abstract
Skin aging is a complex biological process involving intrinsic and extrinsic factors. Skin aging contains alterations at the tissue, cellular, and molecular levels. Currently, there is increasing evidence that skin aging occurs not only in time-dependent chronological aging but also plays a role in skin pigmentary disorders. This review provides an in-depth analysis of the impact of skin aging on different types of pigmentary disorders, including both hyperpigmentation disorders such as melasma and senile lentigo and hypopigmentation disorders such as vitiligo, idiopathic guttate hypomelanosis and graying of hair. In addition, we explore the mechanisms of skin aging on pigmentation regulation and suggest several potential therapeutic approaches for skin aging and aging-related pigmentary disorders.
Collapse
Affiliation(s)
- Yiwen Yang
- Department of Dermatology, Huashan Hospital, Fudan University, No.12 Wulumuqi Zhong Road, Shanghai 200040, PR China
| | - Yue Wu
- Department of Dermatology, Huashan Hospital, Fudan University, No.12 Wulumuqi Zhong Road, Shanghai 200040, PR China
| | - Leihong Xiang
- Department of Dermatology, Huashan Hospital, Fudan University, No.12 Wulumuqi Zhong Road, Shanghai 200040, PR China
| | - Mauro Picardo
- Istituto Dermopatico Immacolata, IDI-RCCS, Rome, Italy.
| | - Chengfeng Zhang
- Department of Dermatology, Huashan Hospital, Fudan University, No.12 Wulumuqi Zhong Road, Shanghai 200040, PR China.
| |
Collapse
|
16
|
Perovic M, Pavlovic D, Palmer Z, Udo MSB, Citadin CT, Rodgers KM, Wu CYC, Zhang Q, Lin HW, Tesic V. Modulation of GABAergic system as a therapeutic option in stroke. Exp Neurol 2025; 384:115050. [PMID: 39522803 DOI: 10.1016/j.expneurol.2024.115050] [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: 07/31/2024] [Revised: 10/18/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Stroke is one of the leading causes of death and permanent adult disability worldwide. Despite the improvements in reducing the rate and mortality, the societal burden and costs of treatment associated with stroke management are increasing. Most of the therapeutic approaches directly targeting ischemic injury have failed to reduce short- and long-term morbidity and mortality and more effective therapeutic strategies are still needed to promote post-stroke functional recovery. Decades of stroke research have been focused on hyperexcitability and glutamate-induced excitotoxicity in the acute phase of ischemia and their relation to motor deficits. Recent advances in understanding the pathophysiology of stroke have been made with several lines of evidence suggesting that changes in the neurotransmission of the major inhibitory system via γ-Aminobutyric acid (GABA) play a particularly important role in functional recovery and deserve further attention. The present review provides an overview of how GABAergic neurotransmission changes correlate with stroke recovery and outlines GABAergic system modulators with special emphasis on neurosteroids that have been shown to affect stroke pathogenesis or plasticity or to protect against cognitive decline. Supporting evidence from both animal and human clinical studies is presented and the potential for GABA signaling-targeted therapies for stroke is discussed to translate this concept to human neural repair therapies. Age and sex are considered crucial parameters related to the pathophysiology of stroke and important factors in the development of therapeutic pharmacological strategies. Future work is needed to deepen our knowledge of the neurochemical changes after stroke, extend the conceptual framework, and allow for the development of more effective interventions that include the modulation of the inhibitory system.
Collapse
Affiliation(s)
- Milka Perovic
- Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Damjan Pavlovic
- Department of Neurology, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Zoe Palmer
- Department of Neurology, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Mariana S B Udo
- Department of Neurology, University of Texas Houston Health Science Center, TX, USA
| | - Cristiane T Citadin
- Department of Neurology, University of Texas Houston Health Science Center, TX, USA
| | - Krista M Rodgers
- Department of Cellular Biology and Anatomy, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Celeste Yin-Chien Wu
- Department of Neurology, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Quanguang Zhang
- Department of Neurology, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Hung Wen Lin
- Department of Neurology, University of Texas Houston Health Science Center, TX, USA
| | - Vesna Tesic
- Department of Neurology, Louisiana State University Health Science Center, Shreveport, LA, USA.
| |
Collapse
|
17
|
Wang GX, Fei WC, Zhi LL, Bai XD, You B. Fermented tea leave extract against oxidative stress and ageing of skin in vitro and in vivo. Int J Cosmet Sci 2025; 47:1-17. [PMID: 39119798 DOI: 10.1111/ics.12976] [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: 11/01/2023] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 08/10/2024]
Abstract
OBJECTIVE The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress. METHODS We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1β, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days. RESULTS Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use. CONCLUSION This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.
Collapse
Affiliation(s)
| | - Wei-Cheng Fei
- R&D Center of Shanghai Huiwen Biotech Co., Ltd, Shanghai, China
| | | | - Xue-Dong Bai
- R&D Center of Shanghai Huiwen Biotech Co., Ltd, Shanghai, China
| | | |
Collapse
|
18
|
Parmar UPS, Surico PL, Mori T, Singh RB, Cutrupi F, Premkishore P, Gallo Afflitto G, Di Zazzo A, Coassin M, Romano F. Antioxidants in Age-Related Macular Degeneration: Lights and Shadows. Antioxidants (Basel) 2025; 14:152. [PMID: 40002339 PMCID: PMC11852319 DOI: 10.3390/antiox14020152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/13/2025] [Accepted: 01/23/2025] [Indexed: 02/27/2025] Open
Abstract
Age-related macular degeneration (AMD) is a leading cause of vision impairment worldwide, primarily driven by oxidative stress and inflammation. This review examines the role of antioxidants in mitigating oxidative damage, emphasizing both their therapeutic potential and limitations in AMD management. Key findings underscore the efficacy of specific antioxidants, including vitamins C and E, lutein, zeaxanthin, and Coenzyme Q10, in slowing AMD progression. Landmark studies such as AREDS and AREDS2 have shaped current antioxidant formulations, although challenges persist, including patient variability and long-term safety concerns. Emerging therapies, such as mitochondrial-targeted antioxidants and novel compounds like saffron and resveratrol, offer promising avenues for AMD treatment. Complementary lifestyle interventions, including antioxidant-rich diets and physical activity, further support holistic management approaches. This review highlights the critical role of antioxidants in AMD therapy, advocating for personalized strategies to optimize patient outcomes.
Collapse
Affiliation(s)
| | - Pier Luigi Surico
- Department of Ophthalmology, Campus Bio-Medico University Hospital, 00128 Rome, Italy
- Department of Sense Organs, La Sapienza University, 00185 Rome, Italy
| | - Tommaso Mori
- Department of Ophthalmology, Campus Bio-Medico University Hospital, 00128 Rome, Italy
| | - Rohan Bir Singh
- Department of Health and Medical Sciences, Adelaide Medical School, Adelaide, SA 5000, Australia
| | - Francesco Cutrupi
- Department of Ophthalmology, Campus Bio-Medico University Hospital, 00128 Rome, Italy
| | - Pramila Premkishore
- Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA
| | - Gabriele Gallo Afflitto
- Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, 00128 Rome, Italy
| | - Antonio Di Zazzo
- Department of Ophthalmology, Campus Bio-Medico University Hospital, 00128 Rome, Italy
| | - Marco Coassin
- Department of Ophthalmology, Campus Bio-Medico University Hospital, 00128 Rome, Italy
| | - Francesco Romano
- Eye Clinic, Department of Biomedical and Clinical Sciences, Ospedale Luigi Sacco, University of Milan, 20157 Milan, Italy
| |
Collapse
|
19
|
Xiao X, Hu M, Gao L, Yuan H, Chong B, Liu Y, Zhang R, Gong Y, Du D, Zhang Y, Yang H, Liu X, Zhang Y, Zhang H, Xu H, Zhao Y, Meng W, Xie D, Lei P, Qi S, Peng Y, Tan T, Yu Y, Hu H, Dong B, Dai L. Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut. Signal Transduct Target Ther 2025; 10:8. [PMID: 39774148 PMCID: PMC11707242 DOI: 10.1038/s41392-024-02094-7] [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: 09/23/2024] [Revised: 12/03/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cys redox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteins modified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved in immunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasing with age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cys modifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signaling pathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidative stress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. This work decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulators of oxidative stress and redox signaling.
Collapse
Affiliation(s)
- Xina Xiao
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Meng Hu
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Li Gao
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Huan Yuan
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Baochen Chong
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Liu
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Rou Zhang
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yanqiu Gong
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Du
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zhang
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Hao Yang
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaohui Liu
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Yan Zhang
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Huiyuan Zhang
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Heng Xu
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Zhao
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Wenbo Meng
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Dan Xie
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Lei
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Shiqian Qi
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Peng
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Tan
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China
| | - Yang Yu
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
| | - Hongbo Hu
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Biao Dong
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Lunzhi Dai
- National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
- Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, China.
| |
Collapse
|
20
|
Lana D, Ugolini F, Iovino L, Attorre S, Giovannini MG. Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression. Front Cell Neurosci 2025; 18:1512985. [PMID: 39835288 PMCID: PMC11743640 DOI: 10.3389/fncel.2024.1512985] [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: 10/17/2024] [Accepted: 12/13/2024] [Indexed: 01/22/2025] Open
Abstract
For over a century after their discovery astrocytes were regarded merely as cells located among other brain cells to hold and give support to neurons. Astrocytes activation, "astrocytosis" or A1 functional state, was considered a detrimental mechanism against neuronal survival. Recently, the scientific view on astrocytes has changed. Accumulating evidence indicate that astrocytes are not homogeneous, but rather encompass heterogeneous subpopulations of cells that differ from each other in terms of transcriptomics, molecular signature, function and response in physiological and pathological conditions. In this review, we report and discuss the recent literature on the phenomic differences of astrocytes in health and their modifications in disease conditions, focusing mainly on the hippocampus, a region involved in learning and memory encoding, in the age-related memory impairments, and in Alzheimer's disease (AD) dementia. The morphological and functional heterogeneity of astrocytes in different brain regions may be related to their different housekeeping functions. Astrocytes that express diverse transcriptomics and phenomics are present in strictly correlated brain regions and they are likely responsible for interactions essential for the formation of the specialized neural circuits that drive complex behaviors. In the contiguous and interconnected hippocampal areas CA1 and CA3, astrocytes show different, finely regulated, and region-specific heterogeneity. Heterogeneous astrocytes have specific activities in the healthy brain, and respond differently to physiological or pathological stimuli, such as inflammaging present in normal brain aging or beta-amyloid-dependent neuroinflammation typical of AD. To become reactive, astrocytes undergo transcriptional, functional, and morphological changes that transform them into cells with different properties and functions. Alterations of astrocytes affect the neurovascular unit, the blood-brain barrier and reverberate to other brain cell populations, favoring or dysregulating their activities. It will be of great interest to understand whether the differential phenomics of astrocytes in health and disease can explain the diverse vulnerability of the hippocampal areas to aging or to different damaging insults, in order to find new astrocyte-targeted therapies that might prevent or treat neurodegenerative disorders.
Collapse
Affiliation(s)
- Daniele Lana
- Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy
| | - Filippo Ugolini
- Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy
| | - Ludovica Iovino
- Institute of Neuroscience, National Research Council (CNR), Pisa, Italy
| | - Selene Attorre
- Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy
| | - Maria Grazia Giovannini
- Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy
| |
Collapse
|
21
|
Kundu S, Kumar V, Arora S, Prasad S, Singh C, Singh A. Nutrition in aging. ESSENTIAL GUIDE TO NEURODEGENERATIVE DISORDERS 2025:415-435. [DOI: 10.1016/b978-0-443-15702-8.00026-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
22
|
Kumar U. Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders. Int J Mol Sci 2024; 26:152. [PMID: 39796008 PMCID: PMC11720483 DOI: 10.3390/ijms26010152] [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: 11/19/2024] [Revised: 12/20/2024] [Accepted: 12/22/2024] [Indexed: 01/13/2025] Open
Abstract
An impact of legalization and decriminalization of marijuana is the gradual increase in the use of cannabis for recreational purposes, which poses a potential threat to society and healthcare systems worldwide. However, the discovery of receptor subtypes, endogenous endocannabinoids, and enzymes involved in synthesis and degradation, as well as pharmacological characterization of receptors, has led to exploration of the use of cannabis in multiple peripheral and central pathological conditions. The role of cannabis in the modulation of crucial events involving perturbed physiological functions and disease progression, including apoptosis, inflammation, oxidative stress, perturbed mitochondrial function, and the impaired immune system, indicates medicinal values. These events are involved in most neurological diseases and prompt the gradual progression of the disease. At present, several synthetic agonists and antagonists, in addition to more than 70 phytocannabinoids, are available with distinct efficacy as a therapeutic alternative in different pathological conditions. The present review aims to describe the use of cannabis in neurological diseases and psychiatric disorders.
Collapse
Affiliation(s)
- Ujendra Kumar
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada
| |
Collapse
|
23
|
Panov AV, Mayorov VI, Dikalov SI. Role of Fatty Acids β-Oxidation in the Metabolic Interactions Between Organs. Int J Mol Sci 2024; 25:12740. [PMID: 39684455 DOI: 10.3390/ijms252312740] [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: 10/25/2024] [Revised: 11/19/2024] [Accepted: 11/24/2024] [Indexed: 12/18/2024] Open
Abstract
In recent decades, several discoveries have been made that force us to reconsider old ideas about mitochondria and energy metabolism in the light of these discoveries. In this review, we discuss metabolic interaction between various organs, the metabolic significance of the primary substrates and their metabolic pathways, namely aerobic glycolysis, lactate shuttling, and fatty acids β-oxidation. We rely on the new ideas about the supramolecular structure of the mitochondrial respiratory chain (respirasome), the necessity of supporting substrates for fatty acids β-oxidation, and the reverse electron transfer via succinate dehydrogenase during β-oxidation. We conclude that ATP production during fatty acid β-oxidation has its upper limits and thus cannot support high energy demands alone. Meanwhile, β-oxidation creates conditions that significantly accelerate the cycle: glucose-aerobic glycolysis-lactate-gluconeogenesis-glucose. Therefore, glycolytic ATP production becomes an important energy source in high energy demand. In addition, lactate serves as a mitochondrial substrate after converting to pyruvate + H+ by the mitochondrial lactate dehydrogenase. All coupled metabolic pathways are irreversible, and the enzymes are organized into multienzyme structures.
Collapse
Affiliation(s)
- Alexander V Panov
- Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31201, USA
| | - Vladimir I Mayorov
- Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31201, USA
| | | |
Collapse
|
24
|
Nguyen HVM, Ran Q, Salmon AB, Bumsoo A, Chiao YA, Bhaskaran S, Richardson A. Mouse models used to test the role of reactive oxygen species in aging and age-related chronic diseases. Free Radic Biol Med 2024; 225:617-629. [PMID: 39419456 PMCID: PMC11624111 DOI: 10.1016/j.freeradbiomed.2024.10.269] [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: 06/10/2024] [Revised: 08/13/2024] [Accepted: 10/02/2024] [Indexed: 10/19/2024]
Abstract
With the development of the technology to generate transgenic and knockout mice in the 1990s, investigators had a powerful tool to directly test the impact of altering a specific gene on a biological process or disease. Over the past three decades, investigators have used transgenic and knockout mouse models, which have altered expression of antioxidant genes, to test the role of oxidative stress/damage in aging and age-related diseases. In this comprehensive review, we describe the studies using transgenic and knockout mouse models to test the role of oxidative stress/damage in aging (longevity) and three age-related diseases, e.g., sarcopenia, cardiac aging, and Alzheimer's Disease. While longevity was consistently altered only by one transgenic and one knockout mouse model as predicted by the Oxidative Stress Theory of Aging, the incidence/progression of the three age-related diseases (especially Alzheimer's disease) were robustly impacted when the expression of various antioxidant genes was altered using transgenic and knockout mouse models.
Collapse
Affiliation(s)
- Hoang Van M Nguyen
- Department of Nutritional Sciences, University of Oklahoma Health Sciences, Oklahoma City, OK, USA
| | - Qitao Ran
- Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; VA South Texas Health Care System, San Antonio, TX, USA
| | - Adam B Salmon
- Department of Molecular Medicine, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; VA South Texas Health Care System, San Antonio, TX, USA
| | - Ahn Bumsoo
- Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Ying Ann Chiao
- Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - Shylesh Bhaskaran
- Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - Arlan Richardson
- Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; VA Oklahoma Health Care System, Oklahoma City, OK, USA.
| |
Collapse
|
25
|
Cornwell AB, Zhang Y, Thondamal M, Johnson DW, Thakar J, Samuelson AV. The C. elegans Myc-family of transcription factors coordinate a dynamic adaptive response to dietary restriction. GeroScience 2024; 46:4827-4854. [PMID: 38878153 PMCID: PMC11336136 DOI: 10.1007/s11357-024-01197-x] [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: 02/16/2024] [Accepted: 05/08/2024] [Indexed: 06/25/2024] Open
Abstract
Dietary restriction (DR), the process of decreasing overall food consumption over an extended period of time, has been shown to increase longevity across evolutionarily diverse species and delay the onset of age-associated diseases in humans. In Caenorhabditis elegans, the Myc-family transcription factors (TFs) MXL-2 (Mlx) and MML-1 (MondoA/ChREBP), which function as obligate heterodimers, and PHA-4 (orthologous to FOXA) are both necessary for the full physiological benefits of DR. However, the adaptive transcriptional response to DR and the role of MML-1::MXL-2 and PHA-4 remains elusive. We identified the transcriptional signature of C. elegans DR, using the eat-2 genetic model, and demonstrate broad changes in metabolic gene expression in eat-2 DR animals, which requires both mxl-2 and pha-4. While the requirement for these factors in DR gene expression overlaps, we found many of the DR genes exhibit an opposing change in relative gene expression in eat-2;mxl-2 animals compared to wild-type, which was not observed in eat-2 animals with pha-4 loss. Surprisingly, we discovered more than 2000 genes synthetically dysregulated in eat-2;mxl-2, out of which the promoters of down-regulated genes were substantially enriched for PQM-1 and ELT-1/3 GATA TF binding motifs. We further show functional deficiencies of the mxl-2 loss in DR outside of lifespan, as eat-2;mxl-2 animals exhibit substantially smaller brood sizes and lay a proportion of dead eggs, indicating that MML-1::MXL-2 has a role in maintaining the balance between resource allocation to the soma and to reproduction under conditions of chronic food scarcity. While eat-2 animals do not show a significantly different metabolic rate compared to wild-type, we also find that loss of mxl-2 in DR does not affect the rate of oxygen consumption in young animals. The gene expression signature of eat-2 mutant animals is consistent with optimization of energy utilization and resource allocation, rather than induction of canonical gene expression changes associated with acute metabolic stress, such as induction of autophagy after TORC1 inhibition. Consistently, eat-2 animals are not substantially resistant to stress, providing further support to the idea that chronic DR may benefit healthspan and lifespan through efficient use of limited resources rather than broad upregulation of stress responses, and also indicates that MML-1::MXL-2 and PHA-4 may have distinct roles in promotion of benefits in response to different pro-longevity stimuli.
Collapse
Affiliation(s)
- Adam B Cornwell
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
| | - Yun Zhang
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
| | - Manjunatha Thondamal
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
- MURTI Centre and Department of Biotechnology, School of Technology, Gandhi Institute of Technology and Management (GITAM), Visakhapatnam, Andhra Pradesh, 530045, India
| | - David W Johnson
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
- Department of Math and Science, Genesee Community College, One College Rd, Batavia, NY, 14020, USA
| | - Juilee Thakar
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
- Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA
| | - Andrew V Samuelson
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
| |
Collapse
|
26
|
Silvestrini A, Mancini A. The Double-Edged Sword of Total Antioxidant Capacity: Clinical Significance and Personal Experience. Antioxidants (Basel) 2024; 13:933. [PMID: 39199179 PMCID: PMC11351343 DOI: 10.3390/antiox13080933] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/23/2024] [Accepted: 07/30/2024] [Indexed: 09/01/2024] Open
Abstract
Oxidative stress (OS) could be a condition underlying several human diseases, despite the physiological role of reactive oxygen species (oxidative eustress). Therefore, antioxidant compounds could represent a modulatory mechanism for maintaining a proper redox balance and redox signaling. When antioxidants are insufficient or overwhelmed, OS ensues, causing multiple damages at molecular, tissue, and cellular levels. This study focuses on the role of total antioxidant capacity (TAC) as a biomarker to be interpreted according to several clinical scenarios. After a brief description of various assay methods to elucidate terminology and physiopathological roles, we focus on the hormonal influence on TAC in blood plasma and other biological fluids, as different endocrine systems can modulate the antioxidant response. Furthermore, OS characterizes several endocrinopathies through different mechanisms: an inadequate antioxidant response to an increase in reducing equivalents (reductive distress) or a marked consumption of antioxidants (oxidative distress), which leads to low TAC values. An increased TAC could instead represent an adaptive mechanism, suggesting a situation of OS. Hence, the clinical context is fundamental for a correct interpretation of TAC. This review aims to provide the reader with a general overview of oxidative stress in several clinical examples of endocrine relevance, such as metabolic syndrome, non-thyroid illness syndrome, hypopituitarism, and infertility. Finally, the impact of dietary and surgical interventions on TAC in the model of metabolic syndrome is highlighted, along with personal experience.
Collapse
Affiliation(s)
- Andrea Silvestrini
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Mancini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy
| |
Collapse
|
27
|
Reddy BL, Reddy VS, Saier MH. Health Benefits of Intermittent Fasting. Microb Physiol 2024; 34:142-152. [PMID: 38955141 PMCID: PMC11262566 DOI: 10.1159/000540068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 05/27/2024] [Indexed: 07/04/2024]
Abstract
We propose that intermittent fasting (time-restricted eating), in agreement with the conclusions of other biologists, as revealed in recent publications, promotes the achievement of numerous health benefits including the extension of human and animal lifespans. Background: There is evidence, obtained both with animal model systems and with humans, that intermittent fasting has health benefits. These benefits include extended longevity, weight loss, and counteracting various disease conditions. Such procedures positively influence the benefits of human tissue-specific microbiomes and minimize the consequences of organellar apoptosis. Key Messages: In this review, we attempt to summarize the predominant evidence, published in the scientific literature, relevant to the conclusions that in general, and in many specific instances, intermittent fasting has long-term benefits to animals, including humans, with respect to overall and specific organismal health and longevity.
Collapse
Affiliation(s)
- B. Lakshmi Reddy
- Department of Molecular Biology, University of California at San Diego 9500 Gilman Dr. La Jolla, CA 92093-0116 USA
| | | | - Milton H. Saier
- Department of Molecular Biology, University of California at San Diego 9500 Gilman Dr. La Jolla, CA 92093-0116 USA
| |
Collapse
|
28
|
Panyod S, Wu WK, Chang CT, Wada N, Ho HC, Lo YL, Tsai SP, Chen RA, Huang HS, Liu PY, Chen YH, Chuang HL, Shen TCD, Tang SL, Ho CT, Wu MS, Sheen LY. Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice. Commun Biol 2024; 7:749. [PMID: 38902371 PMCID: PMC11190199 DOI: 10.1038/s42003-024-06224-3] [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: 03/24/2023] [Accepted: 04/22/2024] [Indexed: 06/22/2024] Open
Abstract
Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.
Collapse
Affiliation(s)
- Suraphan Panyod
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC
- Center for Food and Biomolecules, National Taiwan University, Taipei, Taiwan, ROC
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
| | - Wei-Kai Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, ROC
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
- Bachelor Program of Biotechnology and Food Nutrition, National Taiwan University, Taipei, Taiwan, ROC
| | - Chih-Ting Chang
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC
| | - Naohisa Wada
- Biodiversity Research Center, Academia Sinica, Taipei, Taiwan, ROC
| | - Han-Chen Ho
- Department of Anatomy, Tzu Chi University, Hualien, Taiwan, ROC
| | - Yi-Ling Lo
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
| | - Sing-Ping Tsai
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, ROC
| | - Rou-An Chen
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC
| | - Huai-Syuan Huang
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC
| | - Po-Yu Liu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC
| | - Yi-Hsun Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
| | - Hsiao-Li Chuang
- National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan, ROC
| | - Ting-Chin David Shen
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sen-Lin Tang
- Biodiversity Research Center, Academia Sinica, Taipei, Taiwan, ROC
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ, USA
| | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
| | - Lee-Yan Sheen
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC.
- Center for Food and Biomolecules, National Taiwan University, Taipei, Taiwan, ROC.
- National Center for Food Safety Education and Research, National Taiwan University, Taipei, Taiwan, ROC.
| |
Collapse
|
29
|
Gosslau A, Ozdogru U, Zachariah E, Li S, Ho CT. Effects of ibuprofen in the ZDF rat model of type 2 diabetes. J Food Drug Anal 2024; 32:227-238. [PMID: 38934691 PMCID: PMC11210472 DOI: 10.38212/2224-6614.3506] [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: 11/20/2023] [Accepted: 04/09/2024] [Indexed: 06/28/2024] Open
Abstract
We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF rats were hyperglycemic, dyslipidemic and expressed proinflammatory markers in contrast to lean controls, thus reflecting the relationship between obesity and chronic inflammation promoting T2D. Chronic treatment with ibuprofen (2-(4-Isobutylphenyl)propanoic acid) was used to study the impact on pathological T2D conditions as compared to metformin (1,1-dimethylbiguanide) treated ZDF as well as lean controls. Ibuprofen decreased A1c but induced a high insulin release with improved glucose tolerance only after early time points (i.g., 15 and 30 min) resulting in a non-significant decline of AUC values and translating into a high HOMA-IR. In addition, ibuprofen significantly lowered cholesterol, free fatty acids and HDL-C. Some of these effects by ibuprofen might be based on its anti-inflammatory effects through inhibition of cytokine/chemokine signaling (i.g., COX-2, ICAM-1 and TNF-α) as measured in whole blood and epididymal adipose tissue by TaqMan and/or upregulation of anti-inflammatory cytokines (i.g., IL-4 and IL-13) by ELISA analysis in blood. In conclusion, our ZDF animal study showed positive effects of ibuprofen against diabetic complications such as inflammation and dyslipidemia but also demonstrated the risk of causing insulin resistance.
Collapse
Affiliation(s)
- Alexander Gosslau
- Department of Science (Biology), City University of New York, BMCC, New York, NY 10007,
USA
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520,
USA
| | - Unsal Ozdogru
- Department of Information and Decisions Sciences, University of Illinois at Chicago, Chicago, IL 60607,
USA
| | | | - Shiming Li
- Huanggang Normal University, College of Life Science, Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Hubei Zhongke Research Institute of Industrial Technology, Huanggang 438000, Hubei Province,
China
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520,
USA
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901-8520,
USA
| |
Collapse
|
30
|
Poljšak B, Milisav I. Decreasing Intracellular Entropy by Increasing Mitochondrial Efficiency and Reducing ROS Formation-The Effect on the Ageing Process and Age-Related Damage. Int J Mol Sci 2024; 25:6321. [PMID: 38928027 PMCID: PMC11203720 DOI: 10.3390/ijms25126321] [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: 04/23/2024] [Revised: 06/01/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
A hypothesis is presented to explain how the ageing process might be influenced by optimizing mitochondrial efficiency to reduce intracellular entropy. Research-based quantifications of entropy are scarce. Non-equilibrium metabolic reactions and compartmentalization were found to contribute most to lowering entropy in the cells. Like the cells, mitochondria are thermodynamically open systems exchanging matter and energy with their surroundings-the rest of the cell. Based on the calculations from cancer cells, glycolysis was reported to produce less entropy than mitochondrial oxidative phosphorylation. However, these estimations depended on the CO2 concentration so that at slightly increased CO2, it was oxidative phosphorylation that produced less entropy. Also, the thermodynamic efficiency of mitochondrial respiratory complexes varies depending on the respiratory state and oxidant/antioxidant balance. Therefore, in spite of long-standing theoretical and practical efforts, more measurements, also in isolated mitochondria, with intact and suboptimal respiration, are needed to resolve the issue. Entropy increases in ageing while mitochondrial efficiency of energy conversion, quality control, and turnover mechanisms deteriorate. Optimally functioning mitochondria are necessary to meet energy demands for cellular defence and repair processes to attenuate ageing. The intuitive approach of simply supplying more metabolic fuels (more nutrients) often has the opposite effect, namely a decrease in energy production in the case of nutrient overload. Excessive nutrient intake and obesity accelerate ageing, while calorie restriction without malnutrition can prolong life. Balanced nutrient intake adapted to needs/activity-based high ATP requirement increases mitochondrial respiratory efficiency and leads to multiple alterations in gene expression and metabolic adaptations. Therefore, rather than overfeeding, it is necessary to fine-tune energy production by optimizing mitochondrial function and reducing oxidative stress; the evidence is discussed in this paper.
Collapse
Affiliation(s)
- Borut Poljšak
- Laboratory of Oxidative Stress Research, Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia;
| | - Irina Milisav
- Laboratory of Oxidative Stress Research, Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia;
- Faculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia
| |
Collapse
|
31
|
Albadrani HM, Chauhan P, Ashique S, Babu MA, Iqbal D, Almutary AG, Abomughaid MM, Kamal M, Paiva-Santos AC, Alsaweed M, Hamed M, Sachdeva P, Dewanjee S, Jha SK, Ojha S, Slama P, Jha NK. Mechanistic insights into the potential role of dietary polyphenols and their nanoformulation in the management of Alzheimer's disease. Biomed Pharmacother 2024; 174:116376. [PMID: 38508080 DOI: 10.1016/j.biopha.2024.116376] [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: 06/22/2023] [Revised: 01/19/2024] [Accepted: 02/28/2024] [Indexed: 03/22/2024] Open
Abstract
Alzheimer's disease (AD) is a very common neurodegenerative disorder associated with memory loss and a progressive decline in cognitive activity. The two major pathophysiological factors responsible for AD are amyloid plaques (comprising amyloid-beta aggregates) and neurofibrillary tangles (consisting of hyperphosphorylated tau protein). Polyphenols, a class of naturally occurring compounds, are immensely beneficial for the treatment or management of various disorders and illnesses. Naturally occurring sources of polyphenols include plants and plant-based foods, such as fruits, herbs, tea, vegetables, coffee, red wine, and dark chocolate. Polyphenols have unique properties, such as being the major source of anti-oxidants and possessing anti-aging and anti-cancerous properties. Currently, dietary polyphenols have become a potential therapeutic approach for the management of AD, depending on various research findings. Dietary polyphenols can be an effective strategy to tackle multifactorial events that occur with AD. For instance, naturally occurring polyphenols have been reported to exhibit neuroprotection by modulating the Aβ biogenesis pathway in AD. Many nanoformulations have been established to enhance the bioavailability of polyphenols, with nanonization being the most promising. This review comprehensively provides mechanistic insights into the neuroprotective potential of dietary polyphenols in treating AD. It also reviews the usability of dietary polyphenol as nanoformulation for AD treatment.
Collapse
Affiliation(s)
- Hind Muteb Albadrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province 34212, Saudi Arabia
| | - Payal Chauhan
- Department of Pharmaceutical Sciences, Maharshi Dayanad University, Rohtak, Haryana 124001, India
| | - Sumel Ashique
- Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur 713212, West Bengal, India
| | - M Arockia Babu
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Danish Iqbal
- Department of Health Information Management, College of Applied Medical Sciences, Buraydah Private Colleges, Buraydah 51418, Saudi Arabia
| | - Abdulmajeed G Almutary
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates
| | - Mosleh Mohammad Abomughaid
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia
| | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
| | - Mohammed Alsaweed
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia.
| | - Munerah Hamed
- Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | | | - Saikat Dewanjee
- Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Saurabh Kumar Jha
- Department of Zoology, Kalindi College, University of Delhi, 110008, India
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates
| | - Petr Slama
- Department of Animal Morphology, Physiology and Genetics, Faculty of AgriSciences, Mendel University in Brno, Brno, Czech Republic.
| | - Niraj Kumar Jha
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Centre of Research Impact and Outcome, Chitkara University, Rajpura- 140401, Punjab, India.; School of Bioengineering & Biosciences, Lovely Professional University, Phagwara 144411, India; Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, India.
| |
Collapse
|
32
|
Hahm JH, Nirmala FS, Ha TY, Ahn J. Nutritional approaches targeting mitochondria for the prevention of sarcopenia. Nutr Rev 2024; 82:676-694. [PMID: 37475189 DOI: 10.1093/nutrit/nuad084] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/22/2023] Open
Abstract
A decline in function and loss of mass, a condition known as sarcopenia, is observed in the skeletal muscles with aging. Sarcopenia has a negative effect on the quality of life of elderly. Individuals with sarcopenia are at particular risk for adverse outcomes, such as reduced mobility, fall-related injuries, and type 2 diabetes mellitus. Although the pathogenesis of sarcopenia is multifaceted, mitochondrial dysfunction is regarded as a major contributor for muscle aging. Hence, the development of preventive and therapeutic strategies to improve mitochondrial function during aging is imperative for sarcopenia treatment. However, effective and specific drugs that can be used for the treatment are not yet approved. Instead studies on the relationship between food intake and muscle aging have suggested that nutritional intake or dietary control could be an alternative approach for the amelioration of muscle aging. This narrative review approaches various nutritional components and diets as a treatment for sarcopenia by modulating mitochondrial homeostasis and improving mitochondria. Age-related changes in mitochondrial function and the molecular mechanisms that help improve mitochondrial homeostasis are discussed, and the nutritional components and diet that modulate these molecular mechanisms are addressed.
Collapse
Affiliation(s)
- Jeong-Hoon Hahm
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
| | - Farida S Nirmala
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
| | - Tae Youl Ha
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
| | - Jiyun Ahn
- Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea
- Department of Food Biotechnology, Korea University of Science and Technology, Daejeon-si, South Korea
| |
Collapse
|
33
|
Pandey T, Wang B, Wang C, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK. LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans. Cell Rep 2024; 43:113899. [PMID: 38446666 PMCID: PMC11019932 DOI: 10.1016/j.celrep.2024.113899] [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: 07/30/2023] [Revised: 01/21/2024] [Accepted: 02/15/2024] [Indexed: 03/08/2024] Open
Abstract
Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.
Collapse
Affiliation(s)
- Taruna Pandey
- Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, CA, USA
| | - Bingying Wang
- Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, CA, USA
| | - Changnan Wang
- Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, CA, USA
| | - Jenny Zu
- Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, CA, USA
| | - Huichao Deng
- Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
| | - Kang Shen
- Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
| | - Goncalo Dias do Vale
- Center for Human Nutrition and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jeffrey G McDonald
- Center for Human Nutrition and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Dengke K Ma
- Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
| |
Collapse
|
34
|
Bartman S, Coppotelli G, Ross JM. Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases. Curr Issues Mol Biol 2024; 46:1987-2026. [PMID: 38534746 DOI: 10.3390/cimb46030130] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 02/27/2024] [Accepted: 02/28/2024] [Indexed: 03/28/2024] Open
Abstract
Mitochondria are thought to have become incorporated within the eukaryotic cell approximately 2 billion years ago and play a role in a variety of cellular processes, such as energy production, calcium buffering and homeostasis, steroid synthesis, cell growth, and apoptosis, as well as inflammation and ROS production. Considering that mitochondria are involved in a multitude of cellular processes, mitochondrial dysfunction has been shown to play a role within several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases, although the underlying mechanisms are not entirely understood. The significant increase in lifespan and increased incidence of age-related diseases over recent decades has confirmed the necessity to understand the mechanisms by which mitochondrial dysfunction impacts the process of aging and age-related diseases. In this review, we will offer a brief overview of mitochondria, along with structure and function of this important organelle. We will then discuss the cause and consequence of mitochondrial dysfunction in the aging process, with a particular focus on its role in inflammation, cognitive decline, and neurodegenerative diseases, such as Huntington's disease, Parkinson's disease, and Alzheimer's disease. We will offer insight into therapies and interventions currently used to preserve or restore mitochondrial functioning during aging and neurodegeneration.
Collapse
Affiliation(s)
- Sydney Bartman
- George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Giuseppe Coppotelli
- George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Jaime M Ross
- George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| |
Collapse
|
35
|
Zhu N, Li Y, Xu M. Beneficial Effects of Small-Molecule Oligopeptides Isolated from Panax Ginseng C. A. Meyer on Cellular Fates in Oxidative Stress-Induced Damaged Human Umbilical Vein Endothelial Cells and PC-12. Int J Mol Sci 2024; 25:2906. [PMID: 38474153 DOI: 10.3390/ijms25052906] [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: 12/29/2023] [Revised: 01/21/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
Cell fate instability is a crucial characteristic of aging and appears to contribute to various age-related pathologies. Exploring the connection between bioactive substances and cell fate stability may offer valuable insights into longevity. Therefore, the objective of this study was to investigate the potential beneficial effects of ginseng oligopeptides (GOPs) isolated from Panax ginseng C. A. Meyer at the cellular level. Disruption of homeostasis of human umbilical vein endothelial cells (HUVECs) and PC-12 was achieved by culturing them in the growth medium supplemented with 200 µM of H2O2, and 25, 50, and 100 µg/mL GOPs for 4 h. Then, they were cultured in a H2O2-free growth medium containing different concentration of GOPs. We found that GOP administration retards the oxidative stress-induced cell instability in HUVECs by increasing cell viability, inhibiting the cell cycle arrest, enhancing telomerase (TE) activity, suppressing oxidative stress and an inflammatory attack, and protecting mitochondrial function. Furthermore, we hypothesized that GOPs may promote mitochondrial biosynthesis by upregulating PGC-1α expression. Similarly, GOPs positively regulated cell stability in PC-12; notably, the protective effect of GOPs on PC-12 mainly occurred through the inhibition of autophagic cell death of neuronal cells, while the protective effect on mitochondria was weak. In conclusion, it is evident that GOPs demonstrate potential beneficial effects in maintaining cell fate stability, thereby potentially contributing to an enhanced health span and overall well-being.
Collapse
Affiliation(s)
- Na Zhu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
- College of Public Health, Inner Mongolia Medical University, Hohhot 010059, China
| | - Yong Li
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing 100191, China
| | - Meihong Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing 100191, China
| |
Collapse
|
36
|
Sijbesma JWA, van Waarde A, Klooster A, Kion I, Slart RHJA, Lammertsma AA, Giacobbo BL, Boersma HH, Dierckx RAJO, van Goor H, Bakker SJL. Caloric restriction reduces proteinuria in male rats with established nephropathy. Physiol Rep 2024; 12:e15942. [PMID: 38439743 PMCID: PMC10912948 DOI: 10.14814/phy2.15942] [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: 12/06/2023] [Revised: 01/15/2024] [Accepted: 01/15/2024] [Indexed: 03/06/2024] Open
Abstract
Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria.
Collapse
Affiliation(s)
- J. W. A. Sijbesma
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - A. van Waarde
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - A. Klooster
- Department of PathologyPathologie FrieslandLeeuwardenThe Netherlands
| | - I. Kion
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - R. H. J. A. Slart
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
- Department of Biomedical Photonic Imaging, Faculty of Science and TechnologyUniversity of TwenteEnschedeThe Netherlands
| | - A. A. Lammertsma
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - B. Lima Giacobbo
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - H. H. Boersma
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
- Department of Clinical Pharmacy and PharmacologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - R. A. J. O. Dierckx
- Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - H. van Goor
- Department of Pathology and Medical BiologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| | - S. J. L. Bakker
- Department of NephrologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
| |
Collapse
|
37
|
Procaccini C, de Candia P, Russo C, De Rosa G, Lepore MT, Colamatteo A, Matarese G. Caloric restriction for the immunometabolic control of human health. Cardiovasc Res 2024; 119:2787-2800. [PMID: 36848376 DOI: 10.1093/cvr/cvad035] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/10/2022] [Accepted: 11/28/2022] [Indexed: 03/01/2023] Open
Abstract
Nutrition affects all physiological processes occurring in our body, including those related to the function of the immune system; indeed, metabolism has been closely associated with the differentiation and activity of both innate and adaptive immune cells. While excessive energy intake and adiposity have been demonstrated to cause systemic inflammation, several clinical and experimental evidence show that calorie restriction (CR), not leading to malnutrition, is able to delay aging and exert potent anti-inflammatory effects in different pathological conditions. This review provides an overview of the ability of different CR-related nutritional strategies to control autoimmune, cardiovascular, and infectious diseases, as tested by preclinical studies and human clinical trials, with a specific focus on the immunological aspects of these interventions. In particular, we recapitulate the state of the art on the cellular and molecular mechanisms pertaining to immune cell metabolic rewiring, regulatory T cell expansion, and gut microbiota composition, which possibly underline the beneficial effects of CR. Although studies are still needed to fully evaluate the feasibility and efficacy of the nutritional intervention in clinical practice, the experimental observations discussed here suggest a relevant role of CR in lowering the inflammatory state in a plethora of different pathologies, thus representing a promising therapeutic strategy for the control of human health.
Collapse
Affiliation(s)
- Claudio Procaccini
- Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Via Sergio Pansini 5, 80131 Naples, Italy
- Unità di Neuroimmunologia, IRCCS-Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy
| | - Paola de Candia
- Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via Sergio Pansini, 80131 Naples, Italy
| | - Claudia Russo
- Unità di Neuroimmunologia, IRCCS-Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy
| | - Giusy De Rosa
- Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via Sergio Pansini, 80131 Naples, Italy
| | - Maria Teresa Lepore
- Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Via Sergio Pansini 5, 80131 Naples, Italy
| | - Alessandra Colamatteo
- Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via Sergio Pansini, 80131 Naples, Italy
| | - Giuseppe Matarese
- Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Via Sergio Pansini 5, 80131 Naples, Italy
- Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Via Sergio Pansini, 80131 Naples, Italy
| |
Collapse
|
38
|
Cadenas-Garrido P, Schonvandt-Alarcos A, Herrera-Quintana L, Vázquez-Lorente H, Santamaría-Quiles A, Ruiz de Francisco J, Moya-Escudero M, Martín-Oliva D, Martín-Guerrero SM, Rodríguez-Santana C, Aragón-Vela J, Plaza-Diaz J. Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification. Antioxidants (Basel) 2024; 13:127. [PMID: 38275652 PMCID: PMC10812581 DOI: 10.3390/antiox13010127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/16/2024] [Accepted: 01/18/2024] [Indexed: 01/27/2024] Open
Abstract
Antioxidant defenses in biological systems ensure redox homeostasis, regulating baseline levels of reactive oxygen and nitrogen species (ROS and RNS). Oxidative stress (OS), characterized by a lack of antioxidant defenses or an elevation in ROS and RNS, may cause a modification of biomolecules, ROS being primarily absorbed by proteins. As a result of both genome and environment interactions, proteomics provides complete information about a cell's proteome, which changes continuously. Besides measuring protein expression levels, proteomics can also be used to identify protein modifications, localizations, the effects of added agents, and the interactions between proteins. Several oxidative processes are frequently used to modify proteins post-translationally, including carbonylation, oxidation of amino acid side chains, glycation, or lipid peroxidation, which produces highly reactive alkenals. Reactive alkenals, such as 4-hydroxy-2-nonenal, are added to cysteine (Cys), lysine (Lys), or histidine (His) residues by a Michael addition, and tyrosine (Tyr) residues are nitrated and Cys residues are nitrosylated by a Michael addition. Oxidative and nitrosative stress have been implicated in many neurodegenerative diseases as a result of oxidative damage to the brain, which may be especially vulnerable due to the large consumption of dioxygen. Therefore, the current methods applied for the detection, identification, and quantification in redox proteomics are of great interest. This review describes the main protein modifications classified as chemical reactions. Finally, we discuss the importance of redox proteomics to health and describe the analytical methods used in redox proteomics.
Collapse
Affiliation(s)
- Paula Cadenas-Garrido
- Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Avda, del Conocimiento s/n, 18016 Armilla, Spain; (P.C.-G.); (A.S.-A.); (A.S.-Q.); (J.R.d.F.); (M.M.-E.)
| | - Ailén Schonvandt-Alarcos
- Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Avda, del Conocimiento s/n, 18016 Armilla, Spain; (P.C.-G.); (A.S.-A.); (A.S.-Q.); (J.R.d.F.); (M.M.-E.)
| | - Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (C.R.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (C.R.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Alicia Santamaría-Quiles
- Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Avda, del Conocimiento s/n, 18016 Armilla, Spain; (P.C.-G.); (A.S.-A.); (A.S.-Q.); (J.R.d.F.); (M.M.-E.)
| | - Jon Ruiz de Francisco
- Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Avda, del Conocimiento s/n, 18016 Armilla, Spain; (P.C.-G.); (A.S.-A.); (A.S.-Q.); (J.R.d.F.); (M.M.-E.)
| | - Marina Moya-Escudero
- Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Avda, del Conocimiento s/n, 18016 Armilla, Spain; (P.C.-G.); (A.S.-A.); (A.S.-Q.); (J.R.d.F.); (M.M.-E.)
| | - David Martín-Oliva
- Department of Cell Biology, Faculty of Science, University of Granada, 18071 Granada, Spain;
| | - Sandra M. Martín-Guerrero
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 9RT, UK
| | - César Rodríguez-Santana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (C.R.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Jerónimo Aragón-Vela
- Department of Health Sciences, Area of Physiology, Building B3, Campus s/n “Las Lagunillas”, University of Jaén, 23071 Jaén, Spain
| | - Julio Plaza-Diaz
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS, Complejo Hospitalario Universitario de Granada, 18071 Granada, Spain
| |
Collapse
|
39
|
Dmytriv TR, Lushchak VI. Gut Microbiome as a Target for Anti-ageing Interventions. Subcell Biochem 2024; 107:307-325. [PMID: 39693030 DOI: 10.1007/978-3-031-66768-8_14] [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] [Indexed: 12/19/2024]
Abstract
Trillions of various microorganisms inhabit the human intestine whilst having myriads of effects on the body. They participate in the metabolism of nutrients, support the work of the immune system, regulate operation of the nervous system, and produce vitamins, short-chain fatty acids, and a number of other compounds necessary for the host. An imbalance or disruption in the normal microbial community is called dysbacteriosis or dysbiosis. This condition is often associated with the occurrence of various pathologies including chronic low-intensity inflammation. The latter is one of the key signs of ageing. In this chapter, we consider the gut microbiome as a target for anti-ageing interventions. In particular, we describe the main functions of the gut microbiome, its changes with ageing, and discuss dysbacteriosis as a trigger of accelerated ageing. We also present anti-ageing interventions such as a diet, nutritional supplements (probiotics, prebiotics, antioxidants), and exercise and how they may affect the microbiome and enable or impede healthy longevity.
Collapse
Affiliation(s)
- Tetiana R Dmytriv
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine
| | - Volodymyr I Lushchak
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine.
- Research and Development University, Ivano-Frankivsk, Ukraine.
| |
Collapse
|
40
|
Nel A, Heber D. Precision Nutrition in Allergy and Immune Function. PRECISION NUTRITION 2024:299-316. [DOI: 10.1016/b978-0-443-15315-0.00005-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
41
|
Liang Y, Chen X, Teng Z, Wang X, Yang J, Liu G. Discovery of a 4-Hydroxy-3'-Trifluoromethoxy-Substituted Resveratrol Derivative as an Anti-Aging Agent. Molecules 2023; 29:86. [PMID: 38202669 PMCID: PMC10779923 DOI: 10.3390/molecules29010086] [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: 10/18/2023] [Revised: 12/14/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
With the intensification of population aging, aging-related diseases are attracting more and more attention, thus, the study of aging mechanisms and anti-aging drugs is becoming increasingly urgent. Resveratrol is a potential candidate as an anti-aging agent, but its low bioavailability limits its application in vivo. In this work, a 4-hydroxy-3'-trifluoromethoxy-substituted resveratrol derivative (4-6), owing to its superior cell accumulation, could inhibit NO production in an inflammatory cell model, inhibit oxidative cytotoxicity, and reduce ROS accumulation and the population of apoptotic cells in an oxidative stress cell model. In D-galactose (D-gal)-stimulated aging mice, 4-6 could reverse liver and kidney damage; protect the serum, brain, and liver against oxidative stress; and increase the body's immunity in the spleen. Further D-gal-induced brain aging studies showed that 4-6 could improve the pathological changes in the hippocampus and the dysfunction of the cholinergic system. Moreover, protein expression related to aging, oxidative stress, and apoptosis in the brain tissue homogenate measured via Western blotting also showed that 4-6 could ameliorate brain aging by protecting against oxidative stress and reducing apoptosis. This work revealed that meta-trifluoromethoxy substituted 4-6 deserved to be further investigated as an effective anti-aging candidate drug.
Collapse
Affiliation(s)
- Yinhu Liang
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
| | - Xi Chen
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
| | - Zhifeng Teng
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
| | - Xuekun Wang
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
| | - Jie Yang
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
- Liaocheng Key Laboratory of Quality Control and Pharmacodynamic Evaluation of Ganoderma Lucidum, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China
| | - Guoyun Liu
- School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China (X.W.)
- Liaocheng Key Laboratory of Quality Control and Pharmacodynamic Evaluation of Ganoderma Lucidum, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China
| |
Collapse
|
42
|
Balaguer F, Barrena M, Enrique M, Maicas M, Álvarez B, Tortajada M, Chenoll E, Ramón D, Martorell P. Bifidobacterium animalis subsp. lactis BPL1™ and Its Lipoteichoic Acid Modulate Longevity and Improve Age/Stress-Related Behaviors in Caenorhabditis elegans. Antioxidants (Basel) 2023; 12:2107. [PMID: 38136226 PMCID: PMC10740966 DOI: 10.3390/antiox12122107] [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: 11/10/2023] [Revised: 11/30/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Life expectancy has increased globally in recent decades, driving interest in maintaining a healthy life that includes preservation of physical and mental abilities, particularly in elderly people. The gut microbiome becomes increasingly perturbed with aging so the use of probiotics can be a strategy for maintaining a balanced gut microbiome. A previous report showed that Bifidobacterium animalis subsp. lactis BPL1™ induces through its lipoteichoic acid (LTA) fat reduction activities via the insulin/IGF-1 signaling pathway. Here, we have delved into the mechanism of action, eliminating alternative pathways as putative mechanisms. Furthermore, we have identified that BPL1™, its heat treated form (BPL1™ HT) and its LTA prolong longevity in Caenorhabditis elegans (C. elegans) in an insulin/IGF-1-dependent mechanism, and its consumption improves the oxidative stress response, gut permeability and protection against pathogenic infections. Furthermore, positive effects on C. elegans stress-related behaviors and in the Alzheimer's Disease model were found, highlighting the potential of the strain in improving the cognitive functions and proteotoxicity in the nematode. These results indicate the pivotal role of the IGF-1 pathway in the activity of the strain and pave the way for potential applications of BPL1™, BPL1™ HT and its LTA in the field of longevity and age-related markers.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Patricia Martorell
- Archer Daniels Midland, Nutrition, Health & Wellness, Biopolis S.L. Parc Científic Universitat de València, C/Catedrático Agustín Escardino Benlloch, 9, 46980 Paterna, Spain (M.B.); (M.E.); (M.T.); (E.C.)
| |
Collapse
|
43
|
Zeidan RS, McElroy T, Rathor L, Martenson MS, Lin Y, Mankowski RT. Sex differences in frailty among older adults. Exp Gerontol 2023; 184:112333. [PMID: 37993077 DOI: 10.1016/j.exger.2023.112333] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/24/2023] [Accepted: 11/14/2023] [Indexed: 11/24/2023]
Abstract
By definition, aging is a natural, gradual and continuous process. On the other hand, frailty reflects the increase in vulnerability to stressors and shortens the time without disease (health span) while longevity refers to the length of life (lifespan). The average life expectancy has significantly increased during the last few decades. A longer lifespan has been accompanied by an increase in frailty and decreased independence in older adults, with major differences existing between men and women. For example, women tend to live longer than men but also experience higher rates of frailty and disability. Sex differences prevent optimization of lifestyle interventions and therapies to effectively prevent frailty. Sex differences in frailty and aging are rooted in a complex interplay between uncontrollable (genetic, epigenetic, physiological), and controllable factors (psychosocial and lifestyle factors). Thus, understanding the underlying causes of sex differences in frailty and aging is essential for developing personalized interventions to promote healthy aging and improve quality of life in older men and women. In this review, we have discussed the key contributors and knowledge gaps related to sex differences in aging and frailty.
Collapse
Affiliation(s)
- Rola S Zeidan
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Taylor McElroy
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Laxmi Rathor
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Matthew S Martenson
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Yi Lin
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Robert T Mankowski
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| |
Collapse
|
44
|
Wang S, Heng K, Song X, Zhai J, Zhang H, Geng Q. Lycopene Improves Bone Quality in SAMP6 Mice by Inhibiting Oxidative Stress, Cellular Senescence, and the SASP. Mol Nutr Food Res 2023; 67:e2300330. [PMID: 37880898 DOI: 10.1002/mnfr.202300330] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 09/17/2023] [Indexed: 10/27/2023]
Abstract
SCOPE Cellular senescence (CS) is closely related to tissue ageing including bone ageing. CS and the senescence-associated secretory phenotype (SASP) have emerged as critical pathogenesis elements of senile osteoporosis. This study aims to investigate the effect of lycopene on senile osteoporosis. METHODS AND RESULTS The senescence-accelerated mouse prone 6 (SAMP6) strain of mice is used as the senile osteoporosis model. Daily ingestion of lycopene for 8 weeks preserves the bone mass, density, strength, and microarchitecture in the SAMP6 mice. Moreover, these alterations are associated with a decrease in oxidative stress in the senile osteoporosis model. In addition, there is a reduction in osteoblast and osteocyte senescence and the SASP in the bone tissues of the SAMP6 mice. Lycopene improves bone health likely due to its antioxidant properties that may be linked with the regulation of CS and SASP in the SAMP6 mice. CONCLUSION These results suggest that lycopene may be beneficial for the management of senile osteoporosis by inhibiting oxidative stress, CS, and the SASP.
Collapse
Affiliation(s)
- Shen Wang
- Key Laboratory of Clinical Research of Osteoporosis, Xuzhou Medical University, Xuzhou, 221300, China
- Central Lab, Pizhou Hospital, Xuzhou Medical University, Xuzhou, 221300, China
- Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, 100044, China
- Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Beijing, 100044, China
- National Center for Trauma Medicine, Beijing, 100044, China
| | - Ke Heng
- Department of Orthopedics, Changzhou Second Hospital, Nanjing Medical University, Changzhou, 213000, China
| | - Xingchen Song
- Key Laboratory of Clinical Research of Osteoporosis, Xuzhou Medical University, Xuzhou, 221300, China
- Central Lab, Pizhou Hospital, Xuzhou Medical University, Xuzhou, 221300, China
| | - Juan Zhai
- Key Laboratory of Clinical Research of Osteoporosis, Xuzhou Medical University, Xuzhou, 221300, China
- Central Lab, Pizhou Hospital, Xuzhou Medical University, Xuzhou, 221300, China
| | - Huanyu Zhang
- Key Laboratory of Clinical Research of Osteoporosis, Xuzhou Medical University, Xuzhou, 221300, China
- Central Lab, Pizhou Hospital, Xuzhou Medical University, Xuzhou, 221300, China
| | - Qinghe Geng
- Key Laboratory of Clinical Research of Osteoporosis, Xuzhou Medical University, Xuzhou, 221300, China
- Central Lab, Pizhou Hospital, Xuzhou Medical University, Xuzhou, 221300, China
| |
Collapse
|
45
|
Cornwell A, Zhang Y, Thondamal M, Johnson DW, Thakar J, Samuelson AV. The C. elegans Myc-family of transcription factors coordinate a dynamic adaptive response to dietary restriction. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.22.568222. [PMID: 38045350 PMCID: PMC10690244 DOI: 10.1101/2023.11.22.568222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Dietary restriction (DR), the process of decreasing overall food consumption over an extended period of time, has been shown to increase longevity across evolutionarily diverse species and delay the onset of age-associated diseases in humans. In Caenorhabditis elegans, the Myc-family transcription factors (TFs) MXL-2 (Mlx) and MML-1 (MondoA/ChREBP), which function as obligate heterodimers, and PHA-4 (orthologous to forkhead box transcription factor A) are both necessary for the full physiological benefits of DR. However, the adaptive transcriptional response to DR and the role of MML-1::MXL-2 and PHA-4 remains elusive. We identified the transcriptional signature of C. elegans DR, using the eat-2 genetic model, and demonstrate broad changes in metabolic gene expression in eat-2 DR animals, which requires both mxl-2 and pha-4. While the requirement for these factors in DR gene expression overlaps, we found many of the DR genes exhibit an opposing change in relative gene expression in eat-2;mxl-2 animals compared to wild-type, which was not observed in eat-2 animals with pha-4 loss. We further show functional deficiencies of the mxl-2 loss in DR outside of lifespan, as eat-2;mxl-2 animals exhibit substantially smaller brood sizes and lay a proportion of dead eggs, indicating that MML-1::MXL-2 has a role in maintaining the balance between resource allocation to the soma and to reproduction under conditions of chronic food scarcity. While eat-2 animals do not show a significantly different metabolic rate compared to wild-type, we also find that loss of mxl-2 in DR does not affect the rate of oxygen consumption in young animals. The gene expression signature of eat-2 mutant animals is consistent with optimization of energy utilization and resource allocation, rather than induction of canonical gene expression changes associated with acute metabolic stress -such as induction of autophagy after TORC1 inhibition. Consistently, eat-2 animals are not substantially resistant to stress, providing further support to the idea that chronic DR may benefit healthspan and lifespan through efficient use of limited resources rather than broad upregulation of stress responses, and also indicates that MML-1::MXL-2 and PHA-4 may have different roles in promotion of benefits in response to different pro-longevity stimuli.
Collapse
Affiliation(s)
- Adam Cornwell
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
| | - Yun Zhang
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
| | - Manjunatha Thondamal
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
- Department of Biological Sciences, GITAM University, Andhra Pradesh, India
| | - David W Johnson
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
- Department of Math and Science, Genesee Community College, One College Rd Batavia, NY 14020, USA
| | - Juilee Thakar
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
- Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
| | - Andrew V Samuelson
- Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
| |
Collapse
|
46
|
Sato K, Saigusa D, Kokubun T, Fujioka A, Feng Q, Saito R, Uruno A, Matsukawa N, Ohno-Oishi M, Kunikata H, Yokoyama Y, Yasuda M, Himori N, Omodaka K, Tsuda S, Maekawa S, Yamamoto M, Nakazawa T. Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma. NPJ AGING 2023; 9:28. [PMID: 37990002 PMCID: PMC10663551 DOI: 10.1038/s41514-023-00124-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 09/22/2023] [Indexed: 11/23/2023]
Abstract
Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.
Collapse
Affiliation(s)
- Kota Sato
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
- Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Daisuke Saigusa
- Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
- Medical Biochemistry, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Taiki Kokubun
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Amane Fujioka
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Qiwei Feng
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Ritsumi Saito
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
- Medical Biochemistry, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Akira Uruno
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
- Medical Biochemistry, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Naomi Matsukawa
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
| | - Michiko Ohno-Oishi
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hiroshi Kunikata
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Yu Yokoyama
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Masayuki Yasuda
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Noriko Himori
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
- Department of Aging Vision Healthcare, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Kazuko Omodaka
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Satoru Tsuda
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Shigeto Maekawa
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Masayuki Yamamoto
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
- Medical Biochemistry, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Toru Nakazawa
- Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
- Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
- Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
- Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
- Department of Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
| |
Collapse
|
47
|
Yin YJ, Zhang YH, Wang Y, Jiang H, Zhang JB, Liang S, Yuan B. Ferulic acid ameliorates the quality of in vitro-aged bovine oocytes by suppressing oxidative stress and apoptosis. Aging (Albany NY) 2023; 15:12497-12512. [PMID: 37944258 PMCID: PMC10683616 DOI: 10.18632/aging.205193] [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: 08/07/2023] [Accepted: 10/08/2023] [Indexed: 11/12/2023]
Abstract
Ferulic acid (FA) is a well-known natural antioxidant that scavenges oxygen free radicals and alleviates oxidative stress. This study investigated the chemopreventive potential of FA against bovine oocyte quality decline during in vitro aging. The results showed that 5 μM FA supplementation decreased the abnormality rate of in vitro-aged bovine oocytes. In addition, FA supplementation effectively improved antioxidant capacity by removing excessive ROS and maintaining intracellular GSH levels and antioxidant enzyme activity. The mitochondrial activity, mitochondrial membrane potential and intracellular ATP levels in aged bovine oocytes were obviously enhanced by FA supplementation. Furthermore, FA supplementation reduced in vitro aging-induced DNA damage and maintained DNA stability in bovine oocytes. Moreover, sperm binding assay showed the number of sperm that bound to the zona pellucida on aged bovine oocytes was significantly higher in the FA supplemented group than in the Aged group. Therefore, FA is beneficial for maintaining in vitro-aged bovine oocyte quality and could become a potential antioxidant for preventing bovine oocyte in vitro aging during in vitro maturation.
Collapse
Affiliation(s)
- Yi-Jing Yin
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Yong-Hong Zhang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Yu Wang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Hao Jiang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Jia-Bao Zhang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Shuang Liang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| | - Bao Yuan
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China
| |
Collapse
|
48
|
Bazin S, Hemmer‐Brepson C, Logez M, Sentis A, Daufresne M. Distinct impacts of feeding frequency and warming on life history traits affect population fitness in vertebrate ectotherms. Ecol Evol 2023; 13:e10770. [PMID: 38020679 PMCID: PMC10667609 DOI: 10.1002/ece3.10770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 11/01/2023] [Accepted: 11/11/2023] [Indexed: 12/01/2023] Open
Abstract
Body size shifts in ectotherms are mostly attributed to the Temperature Size Rule (TSR) stating that warming speeds up initial growth rate but leads to smaller size when food does not limit growth. Investigating the links between temperature, growth, and life history traits is key to understand the adaptive value of TSR, which might be context dependent. In particular, global warming can affect food quantity or quality which is another major driver of growth, fecundity, and survival. However, we have limited information on how temperature and food jointly influence life history traits in vertebrate predators and how changes in different life history traits combine to influence fitness and population demography. We investigate (1) whether TSR is maintained under different food conditions, (2) if food exacerbates or dampens the effects of temperature on growth and life history traits and (3) if food influences the adaptive value of TSR. We combine experiments on the medaka with Integral Projection Models to scale from life history traits to fitness consequences. Our results confirm that warming triggers a higher initial growth rate and a lower adult size, reduces generation time and increases mean fitness. A lower level of food exacerbates the effects of warming on growth trajectories. Although lower feeding frequency increased survival and decreased fecundity, it did not influence the effects of warming on fish development rates, fecundity, and survival. In contrast, feeding frequency influenced the adaptive value of TSR, as, under intermittent feeding, generation time decreased faster with warming and the increase in growth rate with warming was weaker compared to continuously fed fish. These results are of importance in the context of global warming as resources are expected to change with increasing temperatures but, surprisingly, our results suggest that feeding frequency have a lower impact on fitness at high temperature.
Collapse
Affiliation(s)
- Simon Bazin
- INRAE, Univ. Savoie Mont Blanc, CARRTELThonon‐les‐BainsFrance
- INRAE, Aix Marseille Univ., RECOVERAix‐en‐ProvenceFrance
| | | | - Maxime Logez
- INRAE, Aix Marseille Univ., RECOVERAix‐en‐ProvenceFrance
- INRAE, RIVERLYVilleurbanne CedexFrance
| | - Arnaud Sentis
- INRAE, Aix Marseille Univ., RECOVERAix‐en‐ProvenceFrance
| | | |
Collapse
|
49
|
Zhou W, Tong D, Tian D, Yu Y, Huang L, Zhang W, Yu Y, Lu L, Zhang X, Pan W, Shen J, Shi W, Liu G. Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging. Adv Healthc Mater 2023; 12:e2301799. [PMID: 37611966 DOI: 10.1002/adhm.202301799] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/16/2023] [Indexed: 08/25/2023]
Abstract
Nanoplastics (NPs) may pass through the blood-brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, are assessed in zebrafish with classic T-maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle are evaluated. The results demonstrate that NP-exposed zebrafish takes significantly longer for their first entry and spends markedly less time in the reward zone in the T-maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (β-galactosidase and lipofuscin) are detected in the brains of NP-exposed fish. Along with the accumulation of reactive free radicals, NP-exposed zebrafish suffer significant levels of brain oxidative damage. Furthermore, lower levels of Adenosine triphosphate (ATP) and cyclin-dependent kinase 2 and higher levels of p53 are observed in the brains of NP-exposed zebrafish, suggesting that NPs exposure also results in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.
Collapse
Affiliation(s)
- Weishang Zhou
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Difei Tong
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Dandan Tian
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Yingying Yu
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Lin Huang
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Weixia Zhang
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Yihan Yu
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Lingzheng Lu
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Xunyi Zhang
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Wangqi Pan
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Jiawei Shen
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Wei Shi
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Guangxu Liu
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| |
Collapse
|
50
|
Xie Q, Liu H, Wen S, Wang X, Bing W, Ji W, Zhao B, Ozaki Y, Song W. SERS Tracking Oxidative Stress on a Metalloporphyrin Framework by Vitamin C. Anal Chem 2023; 95:15333-15341. [PMID: 37793058 DOI: 10.1021/acs.analchem.3c02935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2023]
Abstract
Accurate control of charge transfer is crucial to investigate the catalytic reaction mechanism of the biological oxidation process that biomedicine participates in. Herein, we have established an assembly model of metalloporphyrin framework (MPF) nanosheets as the active centers of biological enzymes. The introduction of Vitamin C (VC) into the MPF system can precisely modulate its content of charges. The surface-enhanced Raman scattering activity and peroxidase-like catalytic performance are enhanced simultaneously for the first time by manipulating the optimal molar ratio of an MPF to VC and the reaction sequence with target model molecules. We have confirmed that the formation of the intermediate of Fe(2+)-OOH species is specifically enhanced after VC modulation, which indicates that VC can regulate the oxidative stress of the active center of biological enzymes. This discovery not only accurately resolves the mechanism of VC-selective anticancer therapy but also has important significance for the precise treatment of VC synergistic targeting medicines.
Collapse
Affiliation(s)
- Qinhui Xie
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China
- School of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, P. R. China
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, P. R. China
| | - Hao Liu
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Sisi Wen
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Xiaojun Wang
- School of Construction Machinery, Shandong Jiaotong University, Changqing University Science Park, Jinan 250357, P. R. China
| | - Wei Bing
- School of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, P. R. China
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun 130022, P. R. China
| | - Wei Ji
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, P. R. China
| | - Bing Zhao
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Yukihiro Ozaki
- School of Biological and Environmatal Sciences, Kwansei Gakuin University, 1-Gakuen-Uegahara, Sanda, Hyogo 669-1330, Japan
| | - Wei Song
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| |
Collapse
|