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Minuti A, Raffaele I, Scuruchi M, Lui M, Muscarà C, Calabrò M. Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases. Antioxidants (Basel) 2025; 14:554. [PMID: 40427436 DOI: 10.3390/antiox14050554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/28/2025] [Accepted: 05/05/2025] [Indexed: 05/29/2025] Open
Abstract
Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.
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Affiliation(s)
- Aurelio Minuti
- IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
| | - Ivana Raffaele
- IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
| | - Michele Scuruchi
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Maria Lui
- IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
| | - Claudia Muscarà
- IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
| | - Marco Calabrò
- IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
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Tanaka T, Rosano C, Huang X, Tian Q, Landman BA, Moore AZ, Miljkovic I, Perry A, Khan S, Kalhan R, Carr JJ, Terry JG, Yaffe K, Walker KA, Candia J, Ferrucci L. Plasma proteomic analysis of intermuscular fat links muscle integrity with processing speed in older adults. Alzheimers Dement 2025; 21:e70261. [PMID: 40390202 PMCID: PMC12089079 DOI: 10.1002/alz.70261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 04/02/2025] [Accepted: 04/21/2025] [Indexed: 05/21/2025]
Abstract
INTRODUCTION More intermuscular fat (IMF) has been associated with lower cognitive performance through mechanisms that are not fully elucidated. METHODS The associations of 7628 plasma proteins with IMF were assessed in the Baltimore Longitudinal Study on Aging (n = 941, mean age = 66.7 ± 15.2) and validated in the Coronary Artery Risk Development in Young Adults Study (n = 2451, mean age = 50.2 ± 3.6). Processing speed was assessed by Digit Symbol Substitution Test (DSST). Associations between the main exposures, outcome, and mediators were evaluated using linear regression, and mediating effects were assessed by causal mediation analysis. RESULTS There were 722 plasma proteins associated with IMF in both the discovery and replication cohorts (false discovery rate [FDR] adjusted p ≤ 0.05). Of these, 26 mediated the relationship between IMF and DSST, with effects ranging from 2.8% to 20.9% (p ≤ 0.05). These proteins represented synaptic function and organization, and growth factor binding (FDR adjusted p ≤ 0.05). DISCUSSION Reducing IMF may improve processing speed through effects on growth factor and synaptic activity. HIGHLIGHTS Higher intermuscular fat is associated with lower processing speed, consistently across populations that represent different demographic characteristics. There is a robust plasma proteomic profile of intermuscular fat that is assessed in the abdominal and thigh skeletal muscle. The proteins associated with intermuscular fat reflect signals that are reflective of synaptic function and organization, as well as other molecular pathways such as growth factor binding. Circulating proteins partially explain the association between higher intermuscular fat and lower processing speed, suggesting that higher intermuscular fat effects processing speed through pathways including synaptic functions and growth factor binding.
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Affiliation(s)
- Toshiko Tanaka
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIABaltimoreMarylandUSA
| | - Caterina Rosano
- Department of Epidemiology, School of Public HealthUniversity of PittsburghPittsburghPennsylvaniaUSA
| | - Xiaoning Huang
- Division of Cardiology, Department of Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
| | - Qu Tian
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIABaltimoreMarylandUSA
| | - Bennett A. Landman
- Department of Computer ScienceVanderbilt UniversityNashvilleTennesseeUSA
| | - Ann Z. Moore
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIABaltimoreMarylandUSA
| | - Iva Miljkovic
- Department of Epidemiology, School of Public HealthUniversity of PittsburghPittsburghPennsylvaniaUSA
| | - Andrew Perry
- Vanderbilt Translational and Clinical Cardiovascular Research CenterVanderbilt University School of MedicineNashvilleTennesseeUSA
| | - Sadiya Khan
- Division of Cardiology, Department of Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
| | - Ravi Kalhan
- Division of Pulmonary and Critical Care MedicineDepartment of MedicineNorthwestern University Feinberg School of MedicineChicagoIllinoisUSA
| | - John Jeffrey Carr
- Department of Electrical and Computer EngineeringVanderbilt University School of MedicineNashvilleTennesseeUSA
| | - James G. Terry
- Department of Electrical and Computer EngineeringVanderbilt University School of MedicineNashvilleTennesseeUSA
| | - Kristine Yaffe
- UCSF Weill Institute for NeurosciencesUniversity of California–San FranciscoSan FranciscoCaliforniaUSA
| | - Keenan A. Walker
- Laboratory of Behavioral Neuroscience, National Institute on AgingIntramural Research ProgramBaltimoreMarylandUSA
| | - Julián Candia
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIABaltimoreMarylandUSA
| | - Luigi Ferrucci
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIABaltimoreMarylandUSA
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Li W, Fang W, Zhang Y, Chen Q, Shentu W, Lai Q, Cheng L, Yan S, Kong Q, Qiao S. Research progress on resistance exercise therapy for improving cognitive function in patients with AD and muscle atrophy. Front Aging Neurosci 2025; 17:1552905. [PMID: 40271180 PMCID: PMC12016217 DOI: 10.3389/fnagi.2025.1552905] [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: 12/29/2024] [Accepted: 03/24/2025] [Indexed: 04/25/2025] Open
Abstract
Alzheimer's disease (AD) significantly reduces the quality of life of patients and exacerbates the burden on their families and society. Resistance exercise significantly enhances the overall cognitive function of the elderly and patients with AD while positively improving memory, executive function, and muscle strength, reducing fall risks, and alleviating psychological symptoms. As AD is a neurodegenerative disorder, some nerve factors are readily activated and released during exercise. Therefore, several prior studies have concentrated on exploring the molecular mechanisms of resistance exercise and their impact on brain function and neural plasticity. Recent investigations have identified an intrinsic relationship between individuals with AD and the pathological mechanisms of skeletal muscle atrophy, establishing a correlation between patients with AD cognitive level and skeletal muscle content. Resistance exercise primarily targets the skeletal muscle, which improves cognitive impairment in patients with AD by reducing vascular and neuroinflammatory factors and further enhances cognitive function in patients with AD by restoring the structural function of skeletal muscle. Furthermore, the effects of resistance training vary among distinct subgroups of cognitive impairment. Individuals exhibiting lower cognitive function demonstrate more pronounced adaptive responses in physical performance over time. Consequently, further investigation is warranted to determine whether tailored guidelines-such as variations in the frequency and duration of resistance exercise-should be established for patients with varying levels of dementia, in order to optimize the benefits for those experiencing cognitive impairment. This study aimed to review the relationship between AD and skeletal muscle atrophy, the impact of skeletal muscle atrophy on AD cognition, the mechanism by which resistance exercise improves cognition through skeletal muscle improvement, and the optimal resistance exercise mode to elucidate the additional advantages of resistance exercise in treating cognitive function in patients with AD and skeletal muscle atrophy.
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Affiliation(s)
- Wenyao Li
- Department of Special Inspection, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Wei Fang
- Department of Neurology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Yier Zhang
- Zhejiang Chinese Medical University Hangzhou, Hangzhou, Zhejiang, China
- Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Qiulu Chen
- Department of Neurology, Zhejiang Medical and Health Group Hangzhou Hospital, Hangzhou, Zhejiang, China
| | - Wuyue Shentu
- Zhejiang Chinese Medical University Hangzhou, Hangzhou, Zhejiang, China
| | - Qilun Lai
- Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Lin Cheng
- Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Sicheng Yan
- Liuzhou People's Hospital, Liuzhou, Guangxi, China
| | - Qi Kong
- Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Song Qiao
- Department of Neurology, Zhejiang Hospital, Hangzhou, Zhejiang, China
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Ceccarelli Ceccarelli D, Solerte SB. Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia. Metabolites 2025; 15:159. [PMID: 40137124 PMCID: PMC11943464 DOI: 10.3390/metabo15030159] [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: 12/31/2024] [Revised: 02/22/2025] [Accepted: 02/24/2025] [Indexed: 03/27/2025] Open
Abstract
Background: Aging is characterized by shared cellular and molecular processes, and aging-related diseases might co-exist in a cluster of comorbidities, particularly in vulnerable individuals whose phenotype meets the criteria for frailty. Whilst the multidimensional definition of frailty is still controversial, there is an increasing understanding of the common pathways linking metabolic syndrome, cognitive decline, and sarcopenia, frequent conditions in frail elderly patients. Methods: We performed a systematic search in the electronic databases Cochrane Library and PubMed and included preclinical studies, cohort and observational studies, and trials. Discussion: Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment. Insulin resistance is a cause of synaptic dysfunction and neurodegeneration. Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis. Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health. In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer. The interrelation of metabolic syndrome, sarcopenia, and cognitive decline suggests that targeting these shared metabolic pathways could mitigate all the conditions. Pharmacological interventions, including GLP-1 receptor agonists, metformin, and SIRT 1 inducers, demonstrated neuroprotective effects in animals and some preliminary clinical models. Conclusions: These findings encourage further research on the prevention and treatment of neurodegenerative diseases as well as the drug-repurposing potential of molecules currently approved for diabetes, dyslipidemia, and metabolic syndrome.
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Affiliation(s)
| | - Sebastiano Bruno Solerte
- Geriatric and Diabetology Unit, Department of Internal Medicine, University of Pavia, Corso Strada Nuova 63, 27100 Pavia, Italy;
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Zhang C, Tian Y, Liu X, Yang X, Jiang S, Zhang G, Yang C, Liu W, Guo W, Zhao W, Yin D. MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis. Arch Biochem Biophys 2025; 764:110273. [PMID: 39701202 DOI: 10.1016/j.abb.2024.110273] [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: 12/14/2024] [Accepted: 12/15/2024] [Indexed: 12/21/2024]
Abstract
Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both in vitro and in vivo, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model. Enforced miR-495 expression by its mimic could enormously facilitate the differentiation and regeneration of both mouse myoblast C2C12 cells and muscle satellite cells. Furthermore, MyoD was proved as the directly interacted gene of miR-495, and their interaction was crucial for myotube formation. Enforced miR-495 expression could intensively strengthen the muscle mass, in situ muscular electrophysiological indexes, including peak tetanic tension (Po) and peak twitch tension (Pt), and the cross-sectional areas (CSA) of muscle fibers via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 signaling pathway, indicating that miR-495 can be proposed as an effective target for muscle atrophy treatment induced by in the mechanical unloading, random rotating and aging.
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Affiliation(s)
- Chenyan Zhang
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518063, China; Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China.
| | - Yile Tian
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518063, China; Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Xinli Liu
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Xuezhou Yang
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Shanfeng Jiang
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Ge Zhang
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518063, China; Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Changqing Yang
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Wenjing Liu
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Weihong Guo
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518063, China; Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Wenzhe Zhao
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Dachuan Yin
- Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China.
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Tanaka T, Rosano C, Huang X, Tian Q, Landman BA, Moore AZ, Miljkovic I, Perry A, Khan S, Kalhan R, Carr JJ, Terry JG, Yaffe K, Walker K, Candia J, Ferrucci L. Plasma proteomic analysis of intermuscular fat links muscle integrity with processing speed in older adults. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.01.24.25320976. [PMID: 39974123 PMCID: PMC11838923 DOI: 10.1101/2025.01.24.25320976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
INTRODUCTION More intermuscular fat (IMF) has been associated with lower cognitive performance and faster age-associated decline in cognitive function however, the mechanisms driving this relationship have not been fully elucidated. We utilized proteomic analyses to identify the molecular mediators of the association between IMF and cognition to gain further insight into the mechanisms underlying this association. METHODS In this cross-sectional study, the plasma proteomic profile of IMF was assessed in the Baltimore Longitudinal Study on Aging (BLSA; n=941, age=66.7±15.2) and validated in the Coronary Artery Risk Development in Young Adults Study (CARDIA; n=2451, age=50.2±3.6). The 7628 plasma proteins were assessed using an aptamer-based assay and tested for association with IMF from the thigh (BLSA) and abdomen (CARDIA). Processing speed assessed by Digit Symbol Substitution Test (DSST). Associations between the main exposures, outcome and mediators were evaluated using linear regression, and mediating effects were assessed by causal mediation analysis adjusting for age, sex, muscle area or muscle volume, self-reported race, and years of education. RESULTS Higher IMF was associated with lower DSST performance both in the BLSA and CARDIA studies. There were 722 plasma proteins associated with IMF in both the discovery and replication cohorts (FDR-adjusted p≤0.05). Of the 722 IMF-associated proteins, 26 (24 unique proteins) mediated the relationship between IMF and processing speed with mediation effects ranging from 2.8 to 20.9% (p≤0.05). Overrepresentation analysis of the IMF-associated proteins showed enrichment of proteins in synaptic function and organization, and growth factor binding (FDR-adjusted p≤0.05). DISCUSSION There is a robust proteomic signature explaining, at least in part, the link of IMF with DSST. This signature reflected neurological function and growth factor regulation, which are both implicated in lower processing speed. Reducing IMF through behavioral or pharmacological intervention may improve cognition through reduction in growth factor activity and improvements in synaptic activity.
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Affiliation(s)
- Toshiko Tanaka
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIA, 251 Bayview Boulevard, Baltimore MD, 21224, USA
| | - Caterina Rosano
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA
| | - Xiaoning Huang
- Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair, Chicago, IL, 60611
| | - Qu Tian
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIA, 251 Bayview Boulevard, Baltimore MD, 21224, USA
| | - Bennett A. Landman
- Department of Computer Science, Vanderbilt University, 1211 Medical Center Drive, Nashville, TN, 37232, USA
| | - Ann Z Moore
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIA, 251 Bayview Boulevard, Baltimore MD, 21224, USA
| | - Iva Miljkovic
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA
| | - Andrew Perry
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, TN, 37203, USA
| | - Sadiya Khan
- Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair, Chicago, IL, 60611
| | - Ravi Kalhan
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North Saint Clair Street Chicago, IL, 60611, USA
| | - John Jeffrey Carr
- Department of Electrical and Computer Engineering, Vanderbilt University School of Medicine, Nashville, 2301 Vanderbilt Place, TN, 37235, USA
| | - James G. Terry
- Department of Electrical and Computer Engineering, Vanderbilt University School of Medicine, Nashville, 2301 Vanderbilt Place, TN, 37235, USA
| | - Kristine Yaffe
- UCSF Weill Institute for Neurosciences, University of California–San Francisco, San Francisco, 1651 4th St, CA, 94158, USA
| | - Keenan Walker
- Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, 251 Bayview Boulevard, MD 21224, USA
| | - Julián Candia
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIA, 251 Bayview Boulevard, Baltimore MD, 21224, USA
| | - Luigi Ferrucci
- Longitudinal Studies Section, Translational Gerontology Branch, NIH, NIA, 251 Bayview Boulevard, Baltimore MD, 21224, USA
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Pinto A, Haytural H, Loss CM, Alvarez C, Ertas A, Curtis O, Williams AR, Murphy G, Salleng K, Gografe S, Altıntaş A, Kafri T, Barres R, Deshmukh AS, van Praag H. Muscle Cathepsin B treatment improves behavioral and neurogenic deficits in a mouse model of Alzheimer's Disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.20.633414. [PMID: 39896474 PMCID: PMC11785056 DOI: 10.1101/2025.01.20.633414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Muscle secretes factors during exercise that enhance cognition. Myokine Cathepsin B (Ctsb) is linked to memory function, but its role in neurodegenerative disease is unclear. Here we show that AAV-vector-mediated Ctsb overexpression in skeletal muscle in an Alzheimer's Disease (AD) mouse model (APP/PS1), improves motor coordination, memory function and adult hippocampal neurogenesis, while plaque pathology and neuroinflammation remain unchanged. Additionally, in AD mice, Ctsb treatment modifies hippocampal, muscle and plasma proteomic profiles to resemble that of wildtype controls. Conversely, in wildtype mice, Ctsb expression causes memory deficits and results in protein profiles across tissues that are comparable to AD control mice. In AD mice, Ctsb treatment increases the abundance of hippocampal proteins involved in mRNA metabolism and protein synthesis, including those relevant to adult hippocampal neurogenesis and memory function. Furthermore, Ctsb treatment enhances plasma metabolic and mitochondrial processes, and reduces inflammatory responses. In muscle, Ctsb expression elevates protein translation in AD mice, whereas in wildtype mice mitochondrial proteins decrease. Overall, the biological changes in the treatment groups are consistent with effects on memory function. Thus, skeletal muscle Ctsb application has potential as an AD therapeutic intervention.
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Affiliation(s)
- Alejandro Pinto
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Hazal Haytural
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Cássio Morais Loss
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Claudia Alvarez
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Asude Ertas
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Olivia Curtis
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Alyssa R. Williams
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Grayson Murphy
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Ken Salleng
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Sylvia Gografe
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Ali Altıntaş
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Tal Kafri
- Gene Therapy Center, University of North Carolina at Chapel Hill, Thurston-Bowles, NC 27599, USA
| | - Romain Barres
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur & Centre National pour la Recherche Scientifique (CNRS), 06560 Valbonne, France
| | - Atul S. Deshmukh
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Henriette van Praag
- Stiles-Nicholson Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
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Chen X, Wei K, Peng S, Liu N, He L, Wu B, Shi M, Lin Y. Association between physical activity and cognitive function in post-menopausal women with high parity: the chain-mediating effects of nutritional status and depression. BMC Womens Health 2025; 25:27. [PMID: 39825305 PMCID: PMC11748572 DOI: 10.1186/s12905-025-03548-y] [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: 05/13/2024] [Accepted: 01/02/2025] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND It has been reported that the cognitive responses to physical activity (PA) in postmenopausal women vary by parity status, and women with higher parity show a significant association between PA and cognitive function. However, the potential pathways mediating the relationship between PA and cognitive function in women with higher parity remain unclear. The objective of this study was to examine this association in Chinese cohort and further investigate the mediating pathways. METHODS A total of 2296 postmenopausal women were enrolled from the Baoshan District, from April to December 2020. All participant information was collected through interviewer-administered questionnaires or measurements, including personal information, medical history, lifestyle, body mass index (BMI), cognitive function, nutritional status, and depression status. In this cross-sectional study, generalized linear regression models and the chain-mediation analysis were used to examine the relationship between PA and cognitive function and the mediating pathways. RESULTS There was a significant relationship between PA and cognitive function in the high-parity group (≥ three births). In the fully adjusted generalized linear regression model, PA was significantly associated with cognitive function [β: 0.795, 95% confidence interval (CI): 0.251-1.340, P < 0.05]. The chain-mediation analysis showed that depression and nutritional status were two significant mediators, contributing 37.96% of the indirect effect of the overall effect. CONCLUSIONS Our findings suggest that PA is beneficial for women (≥ three births) to maintain cognitive function, and these benefits are mediated by depression and nutritional status.
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Affiliation(s)
- Xiaotong Chen
- Department of Laboratory Medicine, Jing'an District Central Hospital of Shanghai, Jing'an Branch Affiliated to Huashan Hospital, Fudan University, Shanghai, China
| | - Kai Wei
- Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China
| | - Shanshan Peng
- Health Management Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Na Liu
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Leqi He
- Department of Clinical Laboratory Medicine, Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Biying Wu
- Department of Clinical Laboratory Medicine, Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Meifang Shi
- Youyi Road Community Health Service Centre for Baoshan District, Shanghai, 201999, China.
| | - Yong Lin
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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López-Ojeda W, Hurley RA. Myokines and the Brain: A Novel Neuromuscular Endocrine Loop. J Neuropsychiatry Clin Neurosci 2025; 37:A4-4. [PMID: 39812655 DOI: 10.1176/appi.neuropsych.20240173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Affiliation(s)
- Wilfredo López-Ojeda
- Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center and the Research and Academic Affairs Service Line, W. G. Hefner Veterans Affairs Medical Center, Salisbury, N.C. (López-Ojeda, Hurley); Department of Psychiatry and Behavioral Medicine (López-Ojeda, Hurley) and Department of Radiology (Hurley), Wake Forest University School of Medicine, Winston-Salem, N.C
| | - Robin A Hurley
- Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center and the Research and Academic Affairs Service Line, W. G. Hefner Veterans Affairs Medical Center, Salisbury, N.C. (López-Ojeda, Hurley); Department of Psychiatry and Behavioral Medicine (López-Ojeda, Hurley) and Department of Radiology (Hurley), Wake Forest University School of Medicine, Winston-Salem, N.C
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10
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Bondy SC, Wu M. The Critical Role of Autophagy and Phagocytosis in the Aging Brain. Int J Mol Sci 2024; 26:57. [PMID: 39795916 PMCID: PMC11720579 DOI: 10.3390/ijms26010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/16/2024] [Accepted: 12/19/2024] [Indexed: 01/13/2025] Open
Abstract
As the organism ages, there is a decline in effective energy supply, and this retards the ability to elaborate new proteins. The consequences of this are especially marked in the gradual decline in brain function. The senescence of cells and their constituent organelles is ultimately the cause of aging of the entire nervous system. What is less immediately obvious is that brain aging is also accompanied by the failure of catabolic events that lead to the removal of non-functional cells and ineffective subcellular components. The removal of non-working cellular and subcellular elements within the brain is essential in order to allow the appearance of fresh cells and organelles with a full range of capacities. Thus, the maintenance of operative mechanisms for the dispersal of failed tissue components is important, and its diminished capacity with aging is a significant contributory factor to the onset and progression of age-related neurological disorder. This report discusses the mechanisms underlying autophagy and phagocytosis and how these can be adversely modulated as aging proceeds. The means by which the effective recycling of cellular components may be reinstated in the aged brain are considered.
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Affiliation(s)
- Stephen C. Bondy
- Department of Occupational and Environmental Health and Department of Medicine, University of California, Irvine, CA 92697, USA
| | - Meixia Wu
- Evergreen World ADHC, Westminster, CA 92844, USA;
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11
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Lee JJ, Woo HD, Kim JH, Jung EJ, Lee K. Association of sarcopenia, ambient air pollution and cognitive function in a community-dwelling middle-aged and elderly Korean population: a community-based cohort study. BMJ Open 2024; 14:e092448. [PMID: 39638595 PMCID: PMC11624758 DOI: 10.1136/bmjopen-2024-092448] [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: 08/14/2024] [Accepted: 10/17/2024] [Indexed: 12/07/2024] Open
Abstract
OBJECTIVES To investigate the association of sarcopenia, exposure to medium-term to long-term ambient particulate matter 2.5 µm and 10 µm (PM2.5 and PM10) pollution and cognitive function in a community-dwelling cohort of middle-aged and older adults in South Korea. DESIGN A community-based prospective cohort study. SETTING In the Korean Genome and Epidemiology Study (KoGES). PARTICIPANTS The participants were drawn from the seventh follow-up visit conducted between 2015 and 2016 in the KoGES community-based Ansung cohort who had participated in an ageing substudy. OUTCOME MEASURES Cognitive function was evaluated by the Korean version of the Mini-Mental State Examination (K-MMSE) and decreased cognitive function was defined as a K-MMSE score of 23 or less. RESULTS Of the 2274 participants (mean age 70.1 years, 58.3% women and mean annual PM2.5 and PM10 levels of 30.7 and 52.2 μg/m3, respectively), 8.7% (n=197) were sarcopenic, 35.8% (n=814) were possible sarcopenic and 55.5% (n=1263) were non-sarcopenic. The predictors of sarcopenia included body mass index, cognitive function, age, marital status, hypertension and physical activity. Exposure to PM2.5 and PM10 for an average duration of 1 month to 3 years was not selected as a predictor of sarcopenia. Participants with sarcopenia were associated with lower cognitive scores (β=-1.51, p<0.0001) and decreased cognitive function compared with those without sarcopenia (OR 2.34, 95% CI 1.56 to 3.52). Exposure to medium-term and long-term PM2.5 or PM10 was not associated with sarcopenia. The effect modification of PM exposure on the association between sarcopenia and cognitive function was generally not detected. CONCLUSIONS In this community-based observational cohort study of KoGES participants aged 50 years and older, sarcopenia was associated with decreased cognitive function. However, medium-term to long-term exposure to PM2.5 or PM10 was not associated with sarcopenia and did not modify the relationship between sarcopenia and cognitive function.
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Affiliation(s)
- Jane J Lee
- Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, The Republic of Korea
- Department of Food and Nutrition, College of Human Ecology, Sookmyung Women’s University, Seoul, The Republic of Korea
| | - Hae Dong Woo
- Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, The Republic of Korea
| | - Ji Hyun Kim
- Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, The Republic of Korea
| | - Eun Ju Jung
- Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, The Republic of Korea
| | - Kyoungho Lee
- Division of Population Health Research, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, The Republic of Korea
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12
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Hashmi SA, Sachdeva S, Sindhu U, Tsai C, Bonda K, Keezer M, Zawar I, Punia V. The implications of frailty in older adults with epilepsy. Epilepsia Open 2024; 9:2128-2143. [PMID: 39248297 PMCID: PMC11633683 DOI: 10.1002/epi4.13046] [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: 07/17/2024] [Revised: 08/15/2024] [Accepted: 08/29/2024] [Indexed: 09/10/2024] Open
Abstract
Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management.
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Affiliation(s)
- Syeda Amrah Hashmi
- Department of NeurologyUniversity of Virginia School of MedicineCharlottesvilleVirginiaUSA
| | - Seerat Sachdeva
- Clinical Observer, Epilepsy CenterCleveland ClinicClevelandOhioUSA
| | - Udeept Sindhu
- Clinical Observer, Epilepsy CenterCleveland ClinicClevelandOhioUSA
| | | | | | - Mark Keezer
- Department of NeurosciencesUniversité de MontréalMontrealQuebecCanada
| | - Ifrah Zawar
- Department of NeurologyUniversity of Virginia School of MedicineCharlottesvilleVirginiaUSA
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13
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Kim J, Walk AM, Keye SA, Kinder CJ, Cannavale CN, Burd NA, Khan NA. Adiposity influences intraindividual variability in behavioral and neuroelectric indices of attentional inhibition. Psychophysiology 2024; 61:e14677. [PMID: 39215400 PMCID: PMC11579232 DOI: 10.1111/psyp.14677] [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: 06/28/2023] [Revised: 08/13/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
While overweight or obesity are thought to affect over 70% of the US population, the effects of adiposity on neurocognitive efficiency and stability remain unclear. Intra-individual variability or trial-to-trial variability (IIV) could provide insights into the influence of adiposity on neurophysiological stability. However, previous work examining the association between adiposity and IIV of cognitive outcomes is limited. Thus, this study examined the association between whole-body fat (%BF) and central tendency and IIV metrics of behavioral performance and event-related potentials. Adults (n = 320; 19-64 yrs) completed the Flanker task to assess attentional inhibition with concurrent electroencephalogram recordings to examine the N2 and P3b components. In addition to central tendency outcomes typically reported (i.e., mean accuracy and reaction time [RT]), dispersion outcomes (e.g., standard deviation [SD] of RT, P3b latency, N2 latency, etc.) were also extracted. Upon controlling for age and sex, %BF was inversely associated with (congruent: β = -.18, p = .016; incongruent: β = -.23, p < .001) accuracy. Increasing %BF was related to greater RT SD (congruent: β = .13, p = .032; incongruent: β = .23, p < .001). Furthermore, increased %BF was associated with slower P3b latencies (congruent: β = .21, p = .003; incongruent: β = .18, p = .010), and greater incongruent N2 (β = .16, p = .017) and P3b (β = .16, p = .025) latency SD. These findings suggest adiposity exerts a generalized negative influence on attentional inhibition for both measures of central tendency and dispersion across behavioral and neuroelectric indices.
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Affiliation(s)
- Jeongwoon Kim
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Anne M. Walk
- Department of PsychologyEastern Illinois UniversityCharlestonIllinoisUSA
| | - Shelby A. Keye
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Christopher J. Kinder
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Corinne N. Cannavale
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Nicholas A. Burd
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Naiman A. Khan
- Department of Kinesiology and Community HealthUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
- Division of Nutritional SciencesUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
- Neuroscience ProgramUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
- Beckman Institute for Advanced Science and TechnologyUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
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14
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Sanchez-Martinez Y, Lopez-Lopez JP, Gomez-Montoya I, Hernandez-Quiñones D, Ruiz-Uribe G, Rincón-Rueda Z, Garcia RG, Lopez-Jaramillo P. Muscular strength, endothelial function and cognitive disorders: state of the art. J Physiol 2024. [PMID: 39612371 DOI: 10.1113/jp285939] [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: 09/11/2024] [Accepted: 10/24/2024] [Indexed: 12/01/2024] Open
Abstract
In recent years, the ageing population has increasingly grown. This process carries a range of pathophysiological changes involving alterations in the skeletal muscle, vascular endothelium and brain function, becoming an important risk factor for developing cognitive disorders and cardiovascular diseases. With ageing, there is a decrease in muscle mass and muscle strength, and a relationship between muscle strength decrease and cognitive decline has been shown. Lower handgrip strength has been linked to memory impairment, lower global cognitive function, decreased attention and reduced visuospatial abilities in the elderly, but understanding of the underlying mechanisms that explain the link between altered skeletal muscle function and structure, endothelial dysfunction, and the role of endothelial dysfunction in the onset of cognitive disorders has been scarcely explored. This review aims to detail the cellular and molecular mechanisms by which the progressive changes associated with ageing can alter healthy skeletal muscle and endothelial function, creating an environment of oxidative stress, inflammation and mitochondrial dysfunction. These changes can lead to reduced muscle strength, and the secretion of detrimental endothelial factors, resulting in endothelial dysfunction, blood-brain barrier disruption, and damage to neurons and microglia, ultimately accelerating the onset of cognitive disorders in the elderly. In addition, we aimed to describe the mechanisms that potentially explain how preserving muscular function with resistance training could prevent brain function deterioration, including the production of different factors that allow an improved endothelial function, haemodynamic parameters and brain plasticity, ultimately delaying the onset of cognitive impairment and chronic diseases.
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Affiliation(s)
| | - Jose P Lopez-Lopez
- Masira Research Institute, Universidad de Santander (UDES), Bucaramanga, Colombia
| | | | | | - Gabriela Ruiz-Uribe
- Masira Research Institute, Universidad de Santander (UDES), Bucaramanga, Colombia
| | - Zully Rincón-Rueda
- Masira Research Institute, Universidad de Santander (UDES), Bucaramanga, Colombia
| | - Ronald G Garcia
- Masira Research Institute, Universidad de Santander (UDES), Bucaramanga, Colombia
- Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Patricio Lopez-Jaramillo
- Masira Research Institute, Universidad de Santander (UDES), Bucaramanga, Colombia
- Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
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15
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Lavalle S, Scapaticci R, Masiello E, Messina C, Aliprandi A, Mario Salerno V, Russo A, Pegreffi F. Advancements in sarcopenia diagnosis: from imaging techniques to non-radiation assessments. FRONTIERS IN MEDICAL TECHNOLOGY 2024; 6:1467155. [PMID: 39445171 PMCID: PMC11496100 DOI: 10.3389/fmedt.2024.1467155] [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: 07/19/2024] [Accepted: 09/13/2024] [Indexed: 10/25/2024] Open
Abstract
Sarcopenia is a prevalent condition with significant clinical implications, and it is expected to escalate globally, demanding for effective diagnostic strategies, possibly at an early stage of the disease. Imaging techniques play a pivotal role in comprehensively evaluating sarcopenia, offering insights into both muscle quantity and quality. Among all the imaging techniques currently used for the diagnosis and follow up of sarcopenia, it is possible to distinguish two classes: Rx based techniques, using ionizing radiations, and non-invasive techniques, which are based on the use of safe and low risk diagnostic procedures. Dual-energy x-ray Absorptiometry and Computed Tomography, while widely utilized, entail radiation exposure concerns. Ultrasound imaging offers portability, real-time imaging, and absence of ionizing radiation, making it a promising tool Magnetic Resonance Imaging, particularly T1-weighted and Dixon sequences, provides cross- sectional and high-resolution images and fat-water separation capabilities, facilitating precise sarcopenia quantification. Bioelectrical Impedance Analysis (BIA), a non-invasive technique, estimates body composition, including muscle mass, albeit influenced by hydration status. Standardized protocols, such as those proposed by the Sarcopenia through Ultrasound (SARCUS) Working Group, are imperative for ensuring consistency across assessments. Future research should focus on refining these techniques and harnessing the potential of radiomics and artificial intelligence to enhance diagnostic accuracy and prognostic capabilities in sarcopenia.
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Affiliation(s)
- Salvatore Lavalle
- Department of Medicine and Surgery, Kore University of Enna, Enna, Italy
| | - Rosa Scapaticci
- Institute for the Electromagnetic Sensing of the Environment, National Research Council of Italy, Naples, Italy
| | - Edoardo Masiello
- Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carmelo Messina
- Department of Radiology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | | | | | - Arcangelo Russo
- Department of Medicine and Surgery, Kore University of Enna, Enna, Italy
| | - Francesco Pegreffi
- Department of Medicine and Surgery, Kore University of Enna, Enna, Italy
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16
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Duranti E, Villa C. From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders. BIOLOGY 2024; 13:719. [PMID: 39336146 PMCID: PMC11428675 DOI: 10.3390/biology13090719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/02/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024]
Abstract
Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress. Muscle atrophy and mitochondrial dysfunction are also observed in AD, which may exacerbate cognitive decline due to systemic metabolic dysregulation. PD patients exhibit muscle fiber atrophy, altered muscle composition, and α-synuclein aggregation within muscle cells, contributing to motor symptoms and disease progression. Systemic inflammation and impaired protein degradation pathways are common among these disorders, highlighting muscle tissue as a key player in disease progression. Understanding these muscle-related changes offers potential therapeutic avenues, such as targeting mitochondrial function, reducing inflammation, and promoting muscle regeneration with exercise and pharmacological interventions. This review emphasizes the importance of considering an integrative approach to neurodegenerative disease research, considering both central and peripheral pathological mechanisms, in order to develop more effective treatments and improve patient outcomes.
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Affiliation(s)
| | - Chiara Villa
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy;
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17
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Nascimento MDM, Marques A, Ferrari G, Gouveia ÉR, Ihle A. Longitudinal Associations Between Cognition and Grip Strength, Differentiated by Sex and Physical Activity: A Population-Based Study in Older Adults From 17 European Countries. J Aging Health 2024:8982643241273252. [PMID: 39139082 DOI: 10.1177/08982643241273252] [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: 08/15/2024]
Abstract
Objectives (1) To investigate longitudinal associations between grip strength (GS) and cognition over 4 years in European older adults, (2) to examine differences in temporal associations between men and women and between levels of physical activity, (3) to explore in each year 2015 and 2019 associations between GS quartiles and cognitive performance, and (4) to explore longitudinal associations between GS quartiles (year 2015) and cognitive performance (year 2019). Methods: 25,281 individuals (14,200 women) from 17 European countries aged ≥50 years responded to waves 6th and 8th of the SHARE project. We analyzed GS, a general cognition index, and physical activity level. Results: Panel analyses revealed a bidirectional relationship over 4 years between GS and cognition, with differences between sex, as well as between participants with moderate-to-vigorous and low physical activity levels. Conclusion: Women and participants with low physical activity were more likely to experience cognitive performance deficits 4 years later.
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Affiliation(s)
- Marcelo de Maio Nascimento
- Department of Physical Education, Federal University of Vale do São Francisco, Petrolina, Brazil
- Swiss Center of Expertise in Life Course Research LIVES, Geneva, Switzerland
| | - Adilson Marques
- Swiss Center of Expertise in Life Course Research LIVES, Geneva, Switzerland
- CIPER, Faculdade de Motricidade Humana, Universidade de Lisboa, Lisbon, Portugal
- ISAMB, Universidade de Lisboa, Lisbon, Portugal
| | - Gerson Ferrari
- Escuela de Ciencias de la Actividad Física, el Deporte y la Salud, Universidad de Santiago de Chile(USACH), Santiago, Chile
- Faculty of Health Sciences, Universidad Autónoma de Chile, Providencia, Chile
| | - Élvio Rúbio Gouveia
- Swiss Center of Expertise in Life Course Research LIVES, Geneva, Switzerland
- Department of Physical Education and Sport, University of Madeira, Funchal, Portugal
- Laboratory for Robotics and Engineering System (LARSYS), Interactive Technologies Institute, Funchal, Portugal
| | - Andreas Ihle
- Swiss Center of Expertise in Life Course Research LIVES, Geneva, Switzerland
- Department of Psychology, University of Geneva, Geneva, Switzerland
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
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18
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Li X, Qu X, Shi K, Yang Y, Sun J. Physical exercise for brain plasticity promotion an overview of the underlying oscillatory mechanism. Front Neurosci 2024; 18:1440975. [PMID: 39176382 PMCID: PMC11338794 DOI: 10.3389/fnins.2024.1440975] [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: 05/30/2024] [Accepted: 07/26/2024] [Indexed: 08/24/2024] Open
Abstract
The global recognition of the importance of physical exercise (PE) for human health has resulted in increased research on its effects on cortical activity. Neural oscillations, which are prominent features of brain activity, serve as crucial indicators for studying the effects of PE on brain function. Existing studies support the idea that PE modifies various types of neural oscillations. While EEG-related literature in exercise science exists, a comprehensive review of the effects of exercise specifically in healthy populations has not yet been conducted. Given the demonstrated influence of exercise on neural plasticity, particularly cortical oscillatory activity, it is imperative to consolidate research on this phenomenon. Therefore, this review aims to summarize numerous PE studies on neuromodulatory mechanisms in the brain over the past decade, covering (1) effects of resistance and aerobic training on brain health via neural oscillations; (2) how mind-body exercise affects human neural activity and cognitive functioning; (3) age-Related effects of PE on brain health and neurodegenerative disease rehabilitation via neural oscillation mechanisms; and (4) conclusion and future direction. In conclusion, the effect of PE on cortical activity is a multifaceted process, and this review seeks to comprehensively examine and summarize existing studies' understanding of how PE regulates neural activity in the brain, providing a more scientific theoretical foundation for the development of personalized PE programs and further research.
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Affiliation(s)
| | | | - Kaixuan Shi
- Physical Education Department, China University of Geosciences Beijing, Beijing, China
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19
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Huang S, Chen X, Ding H, Dong B. The relationship between low and asymmetric handgrip strength and low muscle mass: results of a cross-sectional study on health and aging trends in western China. BMC Geriatr 2024; 24:650. [PMID: 39095770 PMCID: PMC11295882 DOI: 10.1186/s12877-024-05199-4] [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: 06/01/2023] [Accepted: 07/03/2024] [Indexed: 08/04/2024] Open
Abstract
OBJECTIVE The aim was to determine the relationship between low handgrip strength (HGS) only, asymmetric HGS only, and low HGS combined with asymmetric HGS and low muscle mass in the West China Health and Aging Trends Study (WCHAT) data. STUDY DESIGN Individuals aged at least 50 years old were included in this cross-sectional study using WCHAT data. Demographic characteristics, such as age, marital status, education level, ethnicity, and drinking and smoking history, as well as chronic diseases, were recorded for all participants. The HGS of both hands was tested three times using a grip dynanometer with the participant in a standing position with arms extended, before recording the maximum value for both hands. The maximum value referred to values < 28 kg and < 18 kg for males and females, respectively. HGS ratios (non-dominant HGS/dominant HGS) of < 0.90 or > 1.10 suggest asymmetric HGS. The subjects were then allocated to the low HGS, asymmetrical HGS, and combined low and asymmetrical HGS (BOTH group) groups, and those with neither low nor asymmetric HGS (the normal group). The InBody 770 instrument was used for the analysis of muscle mass, with low muscle mass defined as a skeletal muscle mass index (SMI) of < 7.0 kg/m2 or < 5.7 kg/m2 for males and females, respectively. The associations between the different HGS groups and low muscle mass were assessed by logistic regression analysis. RESULTS The study included 1748 subjects, of whom 1272 (72.77%) were over the age of 60 years. The numbers of Han, Tibetan, and Qiang were 885 (50.63%), 217 (12.41%), and 579 (33.12%), respectively. A total of 465 individuals (26.60%) were classified as having low muscle mass, while 228 (13.04%), 536 (30.66%), and 125 (7.15%) participants were allocated to the low HGS, asymmetric HGS, and BOTH groups, respectively. The average SMI differed significantly between the normal group and the other groups (normal group vs. asymmetric HGS group vs. low HGS group vs. BOTH group: 6.627 kg/m2 vs. 6.633 kg/m2 vs. 6.492 kg/m2 vs. 5.995 kg/m2, respectively, P < 0.05). In addition, the prevalence of low muscle mass in the normal, asymmetric HGS, low HGS, and BOTH groups increased sequentially, with significant differences (normal group vs. asymmetric HGS group vs. low HGS group vs. BOTH group: 21.5% vs. 22.4% vs. 39.5% vs. 56%, respectively, P = 0.001). Further logistic regression analysis showed that the presence of low HGS (OR = 1.7, 95%CI: 1.203-2.402) and both low and asymmetric HGS (OR = 3.378, 95%CI: 2.173-5.252) were predictive of low muscle mass, with the chance being higher for the latter condition. CONCLUSION The findings suggest that although asymmetrical HGS itself does not increase the chances of low muscle mass. When low HGS and a combination of both features (low HGS combined with asymmetric HGS) is present in subjects, the chance of low muscle mass increases.
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Affiliation(s)
- Sha Huang
- Department of Geriatric, Zigong Affiliated Hospital of Southwest Medical University, Zigong, Sichuan, China
- West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoyan Chen
- Department of Geriatric, Zigong Affiliated Hospital of Southwest Medical University, Zigong, Sichuan, China
- West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, Sichuan Province, China
| | - Huaying Ding
- Department of Geriatric, Zigong Affiliated Hospital of Southwest Medical University, Zigong, Sichuan, China
- West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, Sichuan Province, China
| | - Birong Dong
- Department of Geriatric, Zigong Affiliated Hospital of Southwest Medical University, Zigong, Sichuan, China.
- West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, Sichuan Province, China.
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20
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Nicola L, Loo SJQ, Lyon G, Turknett J, Wood TR. Does resistance training in older adults lead to structural brain changes associated with a lower risk of Alzheimer's dementia? A narrative review. Ageing Res Rev 2024; 98:102356. [PMID: 38823487 DOI: 10.1016/j.arr.2024.102356] [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: 03/10/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
Dementia, particularly Alzheimer's Disease (AD), has links to several modifiable risk factors, especially physical inactivity. When considering the relationship between physcial activity and dementia risk, cognitive benefits are generally attributed to aerobic exercise, with resistance exercise (RE) receiving less attention. This review aims to address this gap by evaluating the impact of RE on brain structures and cognitive deficits associated with AD. Drawing insights from randomized controlled trials (RCTs) utilizing structural neuroimaging, the specific influence of RE on AD-affected brain structures and their correlation with cognitive function are discussed. Preliminary findings suggest that RE induces structural brain changes in older adults that could reduce the risk of AD or mitigate AD progression. Importantly, the impacts of RE appear to follow a dose-response effect, reversing pathological structural changes and improving associated cognitive functions if performed at least twice per week for at least six months, with greatest effects in those already experiencing some element of cognitive decline. While more research is eagerly awaited, this review contributes insights into the potential benefits of RE for cognitive health in the context of AD-related changes in brain structure and function.
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Affiliation(s)
| | | | | | | | - Thomas R Wood
- Department of Pediatrics, University of Washington, Seattle, WA, USA; Institute for Human and Machine Cognition, Pensacola, FL, USA.
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Kim S, Wang S, Kang DW, Um YH, Yoon HM, Lee S, Choe YS, Kim REY, Kim D, Lee CU, Lim HK. Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults. Alzheimers Dement 2024; 20:4868-4878. [PMID: 38889242 PMCID: PMC11247690 DOI: 10.1002/alz.14054] [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: 01/26/2024] [Revised: 05/05/2024] [Accepted: 05/16/2024] [Indexed: 06/20/2024]
Abstract
INTRODUCTION Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aβ) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aβ retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS We identified distinct impacts of three sarcopenia measures on brain structure and Aβ. Muscle mass is mainly associated with Aβ and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.
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Affiliation(s)
- Sunghwan Kim
- Department of PsychiatryYeouido St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Sheng‐Min Wang
- Department of PsychiatryYeouido St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Dong Woo Kang
- Department of PsychiatrySeoul St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Yoo Hyun Um
- Department of PsychiatrySt. Vincent's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Han Min Yoon
- Department of RehabilitationYeouido St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Soyoung Lee
- Department of PsychiatryBrigham and Women's HospitalBostonMassachusettsUSA
- Department of PsychiatryHarvard Medical SchoolBostonMassachusettsUSA
| | | | - Regina EY Kim
- Research InstituteNeurophet Inc.SeoulRepublic of Korea
| | - Donghyeon Kim
- Research InstituteNeurophet Inc.SeoulRepublic of Korea
| | - Chang Uk Lee
- Department of PsychiatrySeoul St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
| | - Hyun Kook Lim
- Department of PsychiatryYeouido St. Mary's Hospital, College of Medicine, The Catholic University of KoreaSeoulRepublic of Korea
- CMC Institute for Basic Medical Sciencethe Catholic Medical Center of The Catholic University of KoreaSeoulRepublic of Korea
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22
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Ibrahim AM, Singh DKA, Ludin AFM, Sakian NIM, Rivan NFM, Shahar S. Cardiovascular risk factors among older persons with cognitive frailty in middle income country. World J Clin Cases 2024; 12:3076-3085. [PMID: 38898873 PMCID: PMC11185391 DOI: 10.12998/wjcc.v12.i17.3076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/11/2024] [Accepted: 04/15/2024] [Indexed: 06/04/2024] Open
Abstract
BACKGROUND Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, represents a multifaceted challenge in the aging population. The role of cardiovascular risk factors in this complex interplay is not yet fully understood. AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia. METHODS A comprehensive approach was employed, with a total of 512 community-dwelling older persons aged 60 years and above, involving two cohorts of older persons from previous studies. Datasets related to cardiovascular risks, namely sociodemographic factors, and cardiovascular risk factors, including hypertension, diabetes, hypercholesterolemia, anthropometric characteristics and biochemical profiles, were pooled for analysis. Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score. Cardiovascular risk was determined using Framingham risk score. Statistical analyses were conducted using SPSS version 21. RESULTS Of the study participants, 46.3% exhibited cognitive frailty. Cardiovascular risk factors including hypertension (OR:1.60; 95%CI: 1.12-2.30), low fat-free mass (OR:0.96; 95%CI: 0.94-0.98), high percentage body fat (OR:1.04; 95%CI: 1.02-1.06), high waist circumference (OR:1.02; 95%CI: 1.01-1.04), high fasting blood glucose (OR:1.64; 95%CI: 1.11-2.43), high Framingham risk score (OR:1.65; 95%CI: 1.17-2.31), together with sociodemographic factors, i.e., being single (OR 3.38; 95%CI: 2.26-5.05) and low household income (OR 2.18; 95%CI: 1.44-3.30) were found to be associated with cognitive frailty. CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty, a prodromal stage of dementia. Early identification and management of cardiovascular risk factors, particularly among specific group of the population might mitigate the risk of cognitive frailty, hence preventing dementia.
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Affiliation(s)
- Azianah Mohamad Ibrahim
- Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Wilayah Persekutuan Kuala Lumpur 50300, Malaysia
| | - Devinder Kaur Ajit Singh
- Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Wilayah Persekutuan Kuala Lumpur 50300, Malaysia
| | - Arimi Fitri Mat Ludin
- Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Wilayah Persekutuan Kuala Lumpur 50300, Malaysia
| | | | - Nurul Fatin Malek Rivan
- Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Wilayah Persekutuan Kuala Lumpur 50300, Malaysia
| | - Suzana Shahar
- Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Wilayah Persekutuan Kuala Lumpur 50300, Malaysia
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23
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Xu J, Zhao X, Guo Q, Yu C, Ding W, Niu J, Zhao J, Zhang L, Zhang S, Qi H, Xi M. Association of physical performance with cognitive impairment in middle-aged to older haemodialysis patients: a multicentre cross-sectional observational study. J Int Med Res 2024; 52:3000605241259439. [PMID: 38867556 PMCID: PMC11179479 DOI: 10.1177/03000605241259439] [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: 12/04/2023] [Accepted: 05/15/2024] [Indexed: 06/14/2024] Open
Abstract
OBJECTIVE To determine the prevalence of cognitive impairment (CI) among middle-aged to older patients receiving maintenance haemodialysis (MHD) and to investigate the potential association between CI and physical performance. METHODS This cross-sectional observational study enrolled participants aged 55-85 years who received MHD. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Physical performance was measured by hand grip strength, the Timed Up and Go Test (TUGT) and the 4-m walking speed. Sociodemographic, clinical and laboratory parameters were recorded for each patient. RESULTS The study included 592 patients (363 males); and of these, 126 (21.3%) were diagnosed with CI. Compared with patients with normal cognitive function, those with CI were significantly older and had significantly longer dialysis duration, lower educational level, higher Malnutrition Inflammation Score, higher depression and higher Charlson Comorbidity Index score. After adjustment for covariates, multiple regression analysis suggested that grip strength (odds ratio [OR] = 0.959, 95% confidence interval [CI] = 0.924, 0.996) and 4-m walking speed (OR = 0.161, 95% CI = 0.070, 0.368) were protective factors. TUGT (OR = 1.037, 95%CI = 1.003, 1.071) was a risk factor. CONCLUSION Physical performance was correlated with CI and might be a significant indicator for the early identification of CI in middle-aged to older MHD patients.
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Affiliation(s)
- Jia Xu
- Department of Nephrology, Pudong New Area People's Hospital, Shanghai, China
| | - Xinhui Zhao
- Department of Nephrology, Pudong New Area People's Hospital, Shanghai, China
| | - Qi Guo
- Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Cheng Yu
- Department of Nephrology, Tongji Hospital School of Medicine, Tongji University, Shanghai, China
| | - Wei Ding
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianying Niu
- Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Junli Zhao
- Department of Nephrology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Liming Zhang
- Department of Nephrology, Zhabei Central Hospital of Jingan District of Shanghai, Shanghai, China
| | - Suhua Zhang
- Department of Nephrology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Jiangsu, China
| | - Hualin Qi
- Department of Nephrology, Pudong New Area People's Hospital, Shanghai, China
| | - Minhui Xi
- Department of Nephrology, Pudong New Area People's Hospital, Shanghai, China
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24
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Huang J, Yan Z, Song Y, Chen T. Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives. Pharmaceutics 2024; 16:651. [PMID: 38794313 PMCID: PMC11125447 DOI: 10.3390/pharmaceutics16050651] [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: 03/30/2024] [Revised: 04/30/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the neuromuscular junction. This condition is characterized by fatigue and muscle weakness, including diplopia, ptosis, and systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, the pathogenesis of MG may involve mitochondrial damage and ferroptosis. Mitochondria are the primary site of energy production, and the reactive oxygen species (ROS) generated due to mitochondrial dysfunction can induce ferroptosis. Nanomedicines have been extensively employed to treat various disorders due to their modifiability and good biocompatibility, but their application in MG management has been rather limited. Nevertheless, nanodrug delivery systems that carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for the treatment of MG. Therefore, this review focuses on various nanoplatforms aimed at attenuating immune dysregulation, restoring mitochondrial function, and inhibiting ferroptosis that could potentially serve as promising agents for targeted MG therapy.
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Affiliation(s)
| | | | - Yafang Song
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (J.H.); (Z.Y.)
| | - Tongkai Chen
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (J.H.); (Z.Y.)
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25
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Yuan Y, Chang J, Sun Q. Research Progress on Cognitive Frailty in Older Adults with Chronic Kidney Disease. Kidney Blood Press Res 2024; 49:302-309. [PMID: 38663363 DOI: 10.1159/000538689] [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: 12/26/2023] [Accepted: 04/01/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND As the medical challenges posed by the ageing population become increasingly severe, the proportion of older people among patients with chronic kidney disease (CKD) is increasing every year. SUMMARY The prevalence of frailty in patients with CKD is significantly higher than that in the general population, and older patients are also a high-risk group for frailty and cognitive impairment. Cognitive frailty, as an important subtype of frailty, is a syndrome characterised by cognitive dysfunction caused by physiological factors, excluding Alzheimer's disease and other types of dementia. It is characterised by the coexistence of physical frailty and cognitive impairment. Previous studies have mainly focused on cognitive impairment, and there is limited research on cognitive frailty, particularly in older patients with CKD. KEY MESSAGES This article provides a comprehensive review of the concept, epidemiology, screening methods, prevention, and treatment measures and possible pathogenesis of cognitive frailty in patients with CKD.
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Affiliation(s)
- Yuqing Yuan
- Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jing Chang
- Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qianmei Sun
- Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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26
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Byfield DC, Stacey BS, Bailey DM. Cognition is selectively impaired in males with spinal pain: A retrospective analysis of data from the Longitudinal Study of Ageing Danish Twins. Exp Physiol 2024; 109:474-483. [PMID: 38367242 PMCID: PMC10988731 DOI: 10.1113/ep091177] [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: 03/05/2023] [Accepted: 01/25/2024] [Indexed: 02/19/2024]
Abstract
Cognitive decline and spinal pain (back pain [BP] and neck pain [NP]) represent a major public health challenge, yet the potential relationship between them remains elusive. A retrospective analysis of the Longitudinal Study of Ageing Danish Twins was performed to determine any potential relationships between BP/NP and cognitive function adjusting for age, sex, educational and socioeconomic status. A total of 4731 adults (2788 females/1943 males) aged 78 ± 6 (SD) years were included in the analysis. We observed a 1-month prevalence of 25% with BP, 21% with NP and 11% for combined BP/NP. While there were no differences in cognition scores for males and females reporting combined BP/NP, compared to those without combined BP/NP (34.38 points [95% confidence interval (CI) = 31.88, 36.88] vs. 35.72 points [95% CI = 35.19, 36.26]; P = 0.180; and 35.72 points [95% CI = 35.19, 36.26] vs. 35.85 points [95% CI = 35.39, 36.31]; P = 0.327; for male and females, respectively), an adjusted analysis revealed that males with combined BP/NP presented with lower cognitive scores compared to males without combined BP/NP (81.26 points [95% CI = 73.80, 88.72] vs. 79.48 points [95% CI = 70.31, 88.66]; P = 0.043). The findings of this hypothesis-generating study may highlight a potential sex-specific association between spinal pain and later-life neurodegeneration.
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Affiliation(s)
- David C. Byfield
- Neurovascular Research Laboratory, Faculty of Life Sciences and EducationUniversity of South WalesPontypriddUK
| | - Benjamin S. Stacey
- Neurovascular Research Laboratory, Faculty of Life Sciences and EducationUniversity of South WalesPontypriddUK
| | - Damian M. Bailey
- Neurovascular Research Laboratory, Faculty of Life Sciences and EducationUniversity of South WalesPontypriddUK
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27
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Wang L, Bian X, Liu L, He Q, Xu J, Chen X, Ye H, Yang J, Jiang L. Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis. Front Endocrinol (Lausanne) 2024; 15:1324867. [PMID: 38559694 PMCID: PMC10981270 DOI: 10.3389/fendo.2024.1324867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 02/28/2024] [Indexed: 04/04/2024] Open
Abstract
Background Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.
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Affiliation(s)
| | | | | | | | | | | | - Hong Ye
- Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Junwei Yang
- Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lei Jiang
- Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
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28
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Ganggaya KS, Vanoh D, Ishak WRW. Prevalence of sarcopenia and depressive symptoms among older adults: a scoping review. Psychogeriatrics 2024; 24:473-495. [PMID: 38105398 DOI: 10.1111/psyg.13060] [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: 05/25/2023] [Revised: 09/19/2023] [Accepted: 11/27/2023] [Indexed: 12/19/2023]
Abstract
Sarcopenia causes a loss of skeletal muscle mass and decreases muscle strength and function. Depressive symptoms are a common cause of distress among geriatrics, significantly affecting the quality of life of older adults. Recently, studies have shown that a correlation exists between sarcopenia and depression. To determine the prevalence of sarcopenia and depressive symptoms and identify the factors associated with sarcopenia, we systematically searched the SCOPUS, Science Direct, and PubMed databases for papers on sarcopenia and depressive symptoms published from 2012 to 2022. We reviewed the literature on sarcopenia, depressive symptom prevalence, the prevalence of subjects with both sarcopenia and depressive symptoms, and the factors associated with sarcopenia. Only cross-sectional studies were included. Nineteen articles met the inclusion criteria for review, with overall sarcopenia prevalence ranging from 3.9% to 41.7%. The prevalence of depressive symptoms was reported in seven studies, ranging from 8.09% to 40%. The most commonly used tools to diagnose sarcopenia and depressive symptoms were the European Working Group on Sarcopenia in Older People consensus and the Geriatric Depression Scale, respectively. Being aged, malnourished, obese, having comorbidities (hypertension and diabetes), having impaired cognitive function, and having polypharmacy were found to be the factors associated with sarcopenia. Sarcopenia and depressive symptoms have been found to cause adverse health outcomes among older people. Appropriate nutritional assessments and interventions should be taken to manage these two geriatric conditions. Further studies should be planned, considering multidomain intervention strategies to improve sarcopenia and older people's mental health.
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Affiliation(s)
- Keerthana Sree Ganggaya
- Nutrition Program, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Divya Vanoh
- Dietetics Program, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Wan Rosli Wan Ishak
- Nutrition Program, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
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29
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Fekete M, Major D, Feher A, Fazekas-Pongor V, Lehoczki A. Geroscience and pathology: a new frontier in understanding age-related diseases. Pathol Oncol Res 2024; 30:1611623. [PMID: 38463143 PMCID: PMC10922957 DOI: 10.3389/pore.2024.1611623] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 02/07/2024] [Indexed: 03/12/2024]
Abstract
Geroscience, a burgeoning discipline at the intersection of aging and disease, aims to unravel the intricate relationship between the aging process and pathogenesis of age-related diseases. This paper explores the pivotal role played by geroscience in reshaping our understanding of pathology, with a particular focus on age-related diseases. These diseases, spanning cardiovascular and cerebrovascular disorders, malignancies, and neurodegenerative conditions, significantly contribute to the morbidity and mortality of older individuals. We delve into the fundamental cellular and molecular mechanisms underpinning aging, including mitochondrial dysfunction and cellular senescence, and elucidate their profound implications for the pathogenesis of various age-related diseases. Emphasis is placed on the importance of assessing key biomarkers of aging and biological age within the realm of pathology. We also scrutinize the interplay between cellular senescence and cancer biology as a central area of focus, underscoring its paramount significance in contemporary pathological research. Moreover, we shed light on the integration of anti-aging interventions that target fundamental aging processes, such as senolytics, mitochondria-targeted treatments, and interventions that influence epigenetic regulation within the domain of pathology research. In conclusion, the integration of geroscience concepts into pathological research heralds a transformative paradigm shift in our understanding of disease pathogenesis and promises breakthroughs in disease prevention and treatment.
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Affiliation(s)
- Monika Fekete
- Department of Public Health, Semmelweis University, Budapest, Hungary
| | - David Major
- Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Agnes Feher
- Department of Public Health, Semmelweis University, Budapest, Hungary
| | | | - Andrea Lehoczki
- Department of Public Health, Semmelweis University, Budapest, Hungary
- Departments of Hematology and Stem Cell Transplantation, South Pest Central Hospital, National Institute of Hematology and Infectious Diseases, Saint Ladislaus Campus, Budapest, Hungary
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30
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Pedrinolla A, Isanejad M, Antognelli C, Bartolini D, Borras C, Cavedon V, Di Sante G, Migni A, Mas-Bargues C, Milanese C, Baschirotto C, Modena R, Pistilli A, Rende M, Schena F, Stabile AM, Telesa NV, Tortorella S, Hemmings K, Vina J, Wang E, McArdle A, Jackson MJ, Venturelli M, Galli F. Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age. BMJ Open 2023; 13:e072291. [PMID: 38135320 DOI: 10.1136/bmjopen-2023-072291] [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] [Indexed: 12/24/2023] Open
Abstract
OBJECTIVE Protein-energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly. METHODS AND ANALYSIS In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the 'Joint Programming Initiative A healthy diet for a healthy life'. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9-1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics. ETHICS AND DISSEMINATION All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects' regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals. TRIAL REGISTRATION NUMBER NCT05343611.
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Affiliation(s)
- Anna Pedrinolla
- Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
| | - Masoud Isanejad
- Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, UK
| | - Cinzia Antognelli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Desirée Bartolini
- Department of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, Perugia, Italy
| | - Consuelo Borras
- Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Valentina Cavedon
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Gabriele Di Sante
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Anna Migni
- Department of Pharmaceutical Sciences, Lipidomics and Micronutrient, University of Perugia, Perugia, Italy
| | - Cristina Mas-Bargues
- Freshage Research Group, Department of Physiology, Faculty of Medicine, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), University of Valencia, Valencia, Spain
| | - Chiara Milanese
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Claudia Baschirotto
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Roberto Modena
- Department of Health and Social Sciences, Molde University College, Molde, Norway
| | - Alessandra Pistilli
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Mario Rende
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Federico Schena
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Anna Maria Stabile
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | | | | | - Kay Hemmings
- Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, UK
| | - Jose Vina
- Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Eivind Wang
- Department of Health and Social Sciences, Molde University College, Molde, Norway
- St Olavs Hospital Trondheim University Hospital, Trondheim, Norway
| | - Anne McArdle
- Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, UK
| | - Malcolm J Jackson
- Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, UK
| | - Massimo Venturelli
- Department of Neuroscience, Biomedicine and Movement (DNBM), University of Verona, Verona, Italy
| | - Francesco Galli
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
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Storoschuk KL, Gharios R, Potter GDM, Galpin AJ, House BT, Wood TR. Strength and multiple types of physical activity predict cognitive function independent of low muscle mass in NHANES 1999–2002. LIFESTYLE MEDICINE 2023; 4. [DOI: 10.1002/lim2.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
AbstractIntroductionMultiple domains of cognitive function decline with age, resulting in a significant burden on quality of life and the healthcare system. Recent studies increasingly point to links between muscle mass, particularly low muscle mass, and risk of cognitive decline. However, complex relationships exist between muscle mass, muscle function, physical activity, and overall health.MethodsData from 1,424 adults 60+ years old in the 1999‐2000 and 2001‐2002 editions of the National Health and Nutrition Examination Survey (NHANES) were used to investigate the relationship between low muscle mass and cognitive function after accounting for strength, physical activity, and nutritional and metabolic risk factors for cognitive decline.ResultsMuscle strength and physical activity independently predicted performance in the digit symbol substitution test, with muscle mass and muscle strength explaining 0.5% and 5% of the variance in cognitive function, respectively. In graphical network analyses, the association between low muscle mass and cognitive function appeared to be primarily mediated by neuromuscular function. Physical activity was associated with strength but, surprisingly, not muscle mass, which was instead more closely related to total mass.ConclusionsLow muscle mass is a relatively poor predictor of cognitive function after accounting for physical activity and strength in older individuals from a representative population dataset in the US. Future studies should account for the way in which muscle mass is accrued, which is likely to confound any association between muscle mass and health outcomes.
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Affiliation(s)
- Kristi L. Storoschuk
- School of Kinesiology and Health Studies Queen's University Kingston Ontario Canada
| | - Ryan Gharios
- Department of Chemical Engineering University of Washington Seattle Washington USA
| | | | - Andrew J. Galpin
- Center for Sport Performance California State University Fullerton California USA
| | | | - Thomas R. Wood
- Department of Pediatrics University of Washington Seattle Washington USA
- Institute for Human and Machine Cognition Pensacola Florida USA
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Li I, Lu T, Lin T, Chen AY, Chu H, Chen Y, Li T, Chen C. Hispidin-enriched Sanghuangporus sanghuang mycelia SS-MN4 ameliorate disuse atrophy while improving muscle endurance. J Cachexia Sarcopenia Muscle 2023; 14:2226-2238. [PMID: 37562939 PMCID: PMC10570085 DOI: 10.1002/jcsm.13307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 05/29/2023] [Accepted: 07/11/2023] [Indexed: 08/12/2023] Open
Abstract
BACKGROUND Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID-19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance. METHODS The effects of Sanghuangporus sanghuang SS-MN4 mycelia were tested on two groups of 6-week-old male mice-one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub-groups: a control group, a group that underwent hind limb casting for 7 days and then recovered for 7 days and a group that was administered with SS-MN4 orally for 14 days, underwent hind limb casting for 7 days and then recovered for 7 days. The fatigue group was divided into two sub-groups: a control group that received no SS-MN4 intervention and an experimental group that was administered with SS-MN4 orally for 39 days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA-seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS-MN4 treatment. RESULTS In a disuse atrophy model induced by hind limb casting, supplementing with 250 mg/kg of SS-MN4 for 14 days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill (P < 0.05). In a fatigue animal model, equivalent SS-MN4 dosage improved swimming (178.7%) and running (162.4%) activities (P < 0.05) and reduced blood urea nitrogen levels by 18% (P < 0.05). SS-MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA-seq and western blot studies from the C2C12 myotube showed that SS-MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage. CONCLUSIONS Supplementation of SS-MN4 (250-mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast-twitch fibre regrowth and fatigue resistance.
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Affiliation(s)
- I‐Chen Li
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Ting‐Yu Lu
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Ting‐Wei Lin
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Andy Y. Chen
- Department of BioengineeringStanford UniversityStanfordCAUSA
| | - Hsin‐Tung Chu
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Yen‐Lien Chen
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Tsung‐Ju Li
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
| | - Chin‐Chu Chen
- Biotech Research InstituteGrape King Bio Ltd.TaoyuanTaiwan
- Institute of Food Science and TechnologyNational Taiwan UniversityTaipeiTaiwan
- Department of Bioscience TechnologyChung Yuan Christian UniversityTaoyuanTaiwan
- Department of Food Science, Nutrition, and Nutraceutical BiotechnologyShih Chien UniversityTaipeiTaiwan
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Lo Re V, Russelli G, Lo Gerfo E, Alduino R, Bulati M, Iannolo G, Terzo D, Martucci G, Anzani S, Panarello G, Sparacia G, Parla G, Avorio F, Raffa G, Pilato M, Speciale A, Agnese V, Mamone G, Tuzzolino F, Vizzini GB, Conaldi PG, Ambrosio F. Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting. Front Neurol 2023; 14:1209905. [PMID: 37693766 PMCID: PMC10486105 DOI: 10.3389/fneur.2023.1209905] [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: 04/24/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023] Open
Abstract
Objective Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition. Methods We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines. Results We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests. Significance We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.
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Affiliation(s)
- Vincenzina Lo Re
- Neurology Service, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), University of Pittsburgh Medical Center (UPMC), Palermo, Italy
| | | | - Emanuele Lo Gerfo
- Neurology Service, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), University of Pittsburgh Medical Center (UPMC), Palermo, Italy
- Department of Research, IRCCS ISMETT, UPMC, Palermo, Italy
| | | | - Matteo Bulati
- Department of Research, IRCCS ISMETT, UPMC, Palermo, Italy
| | | | - Danilo Terzo
- Rehabilitation Service, IRCCS ISMETT, Palermo, Italy
| | - Gennaro Martucci
- Department of Anesthesiology and Intensive Care, IRCCS ISMETT, UPMC, Palermo, Italy
| | - Stefano Anzani
- Neurology Service, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), University of Pittsburgh Medical Center (UPMC), Palermo, Italy
- Department of Research, IRCCS ISMETT, UPMC, Palermo, Italy
| | - Giovanna Panarello
- Department of Anesthesiology and Intensive Care, IRCCS ISMETT, UPMC, Palermo, Italy
| | - Gianvincenzo Sparacia
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT, Palermo, Italy
| | - Giuseppe Parla
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT, Palermo, Italy
| | - Federica Avorio
- Neurology Service, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), University of Pittsburgh Medical Center (UPMC), Palermo, Italy
| | - Giuseppe Raffa
- Cardiac Surgery Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS ISMETT, Palermo, Italy
| | - Michele Pilato
- Cardiac Surgery Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS ISMETT, Palermo, Italy
| | | | | | - Giuseppe Mamone
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT, Palermo, Italy
| | | | | | | | - Fabrisia Ambrosio
- Discovery Center for Musculoskeletal Recovery, Schoen Adams Research Institute at Spaulding, Boston, MA, United States
- Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA, United States
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States
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Vints WAJ, Gökçe E, Langeard A, Pavlova I, Çevik ÖS, Ziaaldini MM, Todri J, Lena O, Sakkas GK, Jak S, Zorba (Zormpa) I, Karatzaferi C, Levin O, Masiulis N, Netz Y. Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis. Front Aging Neurosci 2023; 15:1213057. [PMID: 37520128 PMCID: PMC10374322 DOI: 10.3389/fnagi.2023.1213057] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 06/20/2023] [Indexed: 08/01/2023] Open
Abstract
Background The world's population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise. Method Randomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults' populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996). Discussion Understanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults' populations. Registration Systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).
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Affiliation(s)
- Wouter A. J. Vints
- Department of Health Promotion and Rehabilitation, Lithuanian Sports University, Kaunas, Lithuania
- Department of Rehabilitation Medicine, Research School Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, Netherlands
- Adelante Zorggroep Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, Netherlands
| | - Evrim Gökçe
- Sports Rehabilitation Laboratory, Ankara City Hospital, Ankara, Türkiye
| | | | - Iuliia Pavlova
- Department of Theory and Methods of Physical Culture, Lviv State University of Physical Culture, Lviv, Ukraine
| | | | | | - Jasemin Todri
- Department of Physiotherapy, Universidad Catolica San Antonio (UCAM), Murcia, Spain
| | - Orges Lena
- Department of Physiotherapy, Universidad Catolica San Antonio (UCAM), Murcia, Spain
| | - Giorgos K. Sakkas
- Lifestyle Medicine and Experimental Physiology and Myology Lab, Department of Physical Education and Sports Science, The Center of Research and Evaluation of Human Performance (CREHP), University of Thessaly, National and Kapodistrian University of Athens (TEFAA) Campus, Karyes, Greece
| | - Suzanne Jak
- Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, Netherlands
| | | | - Christina Karatzaferi
- Lifestyle Medicine and Experimental Physiology and Myology Lab, Department of Physical Education and Sports Science, The Center of Research and Evaluation of Human Performance (CREHP), University of Thessaly, National and Kapodistrian University of Athens (TEFAA) Campus, Karyes, Greece
| | - Oron Levin
- Department of Health Promotion and Rehabilitation, Lithuanian Sports University, Kaunas, Lithuania
- Movement Control and Neuroplasticity Research Group, Group Biomedical Sciences, Catholic University of Leuven, Heverlee, Belgium
| | - Nerijus Masiulis
- Department of Health Promotion and Rehabilitation, Lithuanian Sports University, Kaunas, Lithuania
| | - Yael Netz
- Department of Health Promotion and Rehabilitation, Lithuanian Sports University, Kaunas, Lithuania
- The Levinsky-Wingate Academic Center, Wingate Campus, Netanya, Israel
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Damigou E, Kouvari M, Panagiotakos D. The role of skeletal muscle mass on cardiovascular disease risk: an emerging role on modulating lipid profile. Curr Opin Cardiol 2023; 38:352-357. [PMID: 36928171 DOI: 10.1097/hco.0000000000001047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review was to present updated evidence on the role of skeletal muscle mass on cardiometabolic health. RECENT FINDINGS Increased lean, and especially skeletal, muscle mass has been associated with better cardiometabolic health in various epidemiological studies, even in younger age groups. In addition, the link between skeletal muscle mass and adult lipid profile is of interest. A preliminary analysis using the data from the ATTICA prospective cohort study (2002-2022) supports this association. SUMMARY Skeletal muscle mass has many metabolic functions (i.e., glucose, insulin and protein metabolism, mitochondrial function, arterial stiffness, inflammation, oxidative stress, brain function, hormone status). Given its associations with the lipid profile and overall cardiometabolic risk, skeletal muscle mass stands among the emerging risk factors for cardiovascular diseases. In addition to only using body mass index or fat distribution, more studies should evaluate lean mass and its prognostic and predictive ability regarding chronic diseases.
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Affiliation(s)
- Evangelia Damigou
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece
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Boccara E, Golan S, Beeri MS. The association between regional adiposity, cognitive function, and dementia-related brain changes: a systematic review. Front Med (Lausanne) 2023; 10:1160426. [PMID: 37457589 PMCID: PMC10349176 DOI: 10.3389/fmed.2023.1160426] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 05/15/2023] [Indexed: 07/18/2023] Open
Abstract
Background Adiposity has been previously associated with cognitive impairment and Alzheimer's disease and related disorders (ADRD). Body mass index (BMI) is the most common measure of global adiposity, but inconsistent results were found since it is a global measurement. BMI does not represent regional fat distribution which differs between sexes, race, and age. Regional fat distribution may contribute differently to cognitive decline and Alzheimer's disease (AD)-related brain changes. Fat-specific targeted therapies could lead to personalized improvement of cognition. The goal of this systematic review is to explore whether regional fat depots, rather than central obesity, should be used to understand the mechanism underlying the association between adiposity and brain. Methods This systematic review included 33 studies in the English language, conducted in humans aged 18 years and over with assessment of regional adiposity, cognitive function, dementia, and brain measures. We included only studies that have assessed regional adiposity using imaging technics and excluded studies that were review articles, abstract only or letters to editor. Studies on children and adolescents, animal studies, and studies of patients with gastrointestinal diseases were excluded. PubMed, PsychInfo and web of science were used as electronic databases for literature search until November 2022. Results Based on the currently available literature, the findings suggest that different regional fat depots are likely associated with increased risk of cognitive impairment, brain changes and dementia, especially AD. However, different regional fat depots can have different cognitive outcomes and affect the brain differently. Visceral adipose tissue (VAT) was the most studied regional fat, along with liver fat through non-alcoholic fatty liver disease (NAFLD). Pancreatic fat was the least studied regional fat. Conclusion Regional adiposity, which is modifiable, may explain discrepancies in associations of global adiposity, brain, and cognition. Specific regional fat depots lead to abnormal secretion of adipose factors which in turn may penetrate the blood brain barrier leading to brain damage and to cognitive decline.
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Affiliation(s)
- Ethel Boccara
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
| | - Sapir Golan
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Michal Schnaider Beeri
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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Namgung HG, Hong S, Choi YA. Association of Temporalis Muscle Mass with Early Cognitive Impairment in Older Patients with Acute Ischemic Stroke. J Clin Med 2023; 12:4071. [PMID: 37373767 DOI: 10.3390/jcm12124071] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
The prognostic value of temporal muscle mass has been studied in various neurological disorders. Herein, we investigated the association between temporal muscle mass and early cognitive function in patients with acute ischemic stroke. This study included 126 patients with acute cerebral infarction aged ≥65 years. Temporal muscle thickness (TMT) was measured using T2-weighted brain magnetic resonance imaging at admission for acute stroke. Within 2 weeks of stroke onset, skeletal mass index (SMI) and cognitive function were assessed using bioelectrical impedance analysis and the Korean version of the Montreal Cognitive Assessment (MoCA), respectively. Pearson's correlation analyzed the correlation between TMT and SMI, and multiple linear regression analyzed independent predictors of early post-stroke cognitive function. TMT and SMI were significantly positively correlated (R = 0.36, p < 0.001). After adjusting for covariates, TMT was an independent predictor of early post-stroke cognitive function, stratified by the MoCA score (β = 1.040, p = 0.017), age (β = -0.27, p = 0.006), stroke severity (β = -0.298, p = 0.007), and education level (β = 0.38, p = 0.008). TMT may be used as a surrogate marker for evaluating skeletal muscle mass because it is significantly associated with post-stroke cognitive function during the acute phase of ischemic stroke; therefore, TMT may help detect older patients at a high risk of early post-stroke cognitive impairment.
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Affiliation(s)
- Ho-Geon Namgung
- Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Seungho Hong
- Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Young-Ah Choi
- Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Ventura J, Downer B, Li CY, Snih SA. Nativity differences in the relationship between handgrip strength and cognitive impairment in older Mexican Americans over 20 years of follow-up. Arch Gerontol Geriatr 2023; 107:104903. [PMID: 36584560 PMCID: PMC9974812 DOI: 10.1016/j.archger.2022.104903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/01/2022] [Accepted: 12/12/2022] [Indexed: 12/15/2022]
Abstract
PURPOSE To examine nativity differences in the relationship between handgrip strength (HGS) and cognitive impairment among Mexican Americans aged ≥ 65 years with normal or high cognitive function at baseline over a 20-year period. METHODS Prospective cohort study of 2,155 non-institutionalized Mexican Americans aged ≥ 65 years from the Hispanic Established Population for the Epidemiological Study of the Elderly) who scored ≥ 21 in the Mini Mental State Examination (MMSE) at baseline. Measures included socio-demographics, body mass index, medical conditions, depressive symptoms, physical function, disability, HGS quartiles (sex-adjusted), and MMSE. We used generalized estimating equation models to estimate the odds ratio (OR) and 95% Confidence Interval (CI) of cognitive impairment (MMSE < 21) as a function of HGS quartile by nativity and adjusted for covariates. RESULTS US-born and foreign-born participants in the 4th quartile (highest) of HGS at baseline had lower odds of cognitive impairment over time compared with those in the 1st (lowest) HGS quartile (OR=0.95, 95% CI=0.90-0.99 and OR=0.93, 95% CI=0.89-0.98, respectively), after controlling for all covariates. When we analyzed HGS quartiles as time-varying, we found that US-born participants in the 3rd and 4th HGS quartile had 25% and 30% lower odds of cognitive impairment, respectively, while foreign-born participants in the 3rd and 4th HGS quartile had 27% and 49% lower odds of cognitive impairment over time, respectively, after controlling for all covariates. CONCLUSION Foreign-born older Mexican Americans who performed high in HGS experienced 7% lower odds of cognitive impairment over time compared with US-born older Mexican Americans.
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Affiliation(s)
- Juan Ventura
- John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Brian Downer
- Department of Population Health and Health Disparities/School of Public and Population Health, University of Texas Medical Branch, Galveston, TX, USA
| | - Chih-Ying Li
- Department of Occupational Therapy/School of Health Professions, University of Texas Medical Branch, Galveston, TX, USA
| | - Soham Al Snih
- Department of Population Health and Health Disparities/School of Public and Population Health, University of Texas Medical Branch, Galveston, TX, USA; Division of Geriatrics & Palliative Medicine/Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.
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Inada Y, Tohda C. Causal Relationships between Daily Physical Activity, Physical Function, and Cognitive Function Ultimately Leading to Happiness. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3016. [PMID: 36833710 PMCID: PMC9958842 DOI: 10.3390/ijerph20043016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/01/2023] [Accepted: 02/07/2023] [Indexed: 06/18/2023]
Abstract
Frailty is a common age-related condition linked with mobility disorders, long-term care, and death. To prevent frailty, physical activities are considered effective. Several studies have indicated that physical activity can influence mental health as well as body function. Physical activity, cognitive function, and subjective mental health must relate to each other. However, most studies only focus on one-to-one interactions. This observational study aims to clarify the overall relationship and causality between subjective mental health, daily physical activity, and physical and cognitive functions. We recruited 45 people (24 males and 21 females) over 65 years old. Participants visited the university twice and were subjected to activity measurements at home. To examine the causal relationships and related structures between the indicators, structural equation modeling was performed. The results suggest that daily physical activity explains physical function, physical function explains cognitive function, and cognitive function explains subjective mental health, quality of life, and happiness. This study is the first to clarify interactive relationships as an axis that start from daily physical activity to happiness in older adults. Upregulating daily physical activity may improve physical and cognitive functions as well as mental health; this might protect and ameliorate physical, mental, and social frailties.
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Affiliation(s)
| | - Chihiro Tohda
- Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
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Jun L, Robinson M, Geetha T, Broderick TL, Babu JR. Prevalence and Mechanisms of Skeletal Muscle Atrophy in Metabolic Conditions. Int J Mol Sci 2023; 24:ijms24032973. [PMID: 36769296 PMCID: PMC9917738 DOI: 10.3390/ijms24032973] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/29/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Skeletal muscle atrophy is prevalent in a myriad of pathological conditions, such as diabetes, denervation, long-term immobility, malnutrition, sarcopenia, obesity, Alzheimer's disease, and cachexia. This is a critically important topic that has significance in the health of the current society, particularly older adults. The most damaging effect of muscle atrophy is the decreased quality of life from functional disability, increased risk of fractures, decreased basal metabolic rate, and reduced bone mineral density. Most skeletal muscle in humans contains slow oxidative, fast oxidative, and fast glycolytic muscle fiber types. Depending on the pathological condition, either oxidative or glycolytic muscle type may be affected to a greater extent. This review article discusses the prevalence of skeletal muscle atrophy and several mechanisms, with an emphasis on high-fat, high-sugar diet patterns, obesity, and diabetes, but including other conditions such as sarcopenia, Alzheimer's disease, cancer cachexia, and heart failure.
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Affiliation(s)
- Lauren Jun
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Megan Robinson
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Thangiah Geetha
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
| | - Tom L. Broderick
- Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Jeganathan Ramesh Babu
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
- Correspondence: ; Tel.: +1-223-844-3840
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41
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Liu C, Wong PY, Chow SKH, Cheung WH, Wong RMY. Does the regulation of skeletal muscle influence cognitive function? A scoping review of pre-clinical evidence. J Orthop Translat 2023; 38:76-83. [PMID: 36381246 PMCID: PMC9619139 DOI: 10.1016/j.jot.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/25/2022] [Accepted: 10/05/2022] [Indexed: 11/06/2022] Open
Abstract
Background Cognitive impairment is a major challenge for elderlies, as it can progress in a rapid manner and effective treatments are limited. Sarcopenic elderlies have a higher risk of dementia. This scoping review aims to reveal whether muscle is a mediator of cognitive function from pre-clinical evidence. Methods PubMed, Embase, and Web of Science were searched to Feb 2nd, 2022, using the keywords (muscle) AND (cognition OR dementia OR Alzheimer) AND (mouse OR rat OR animal). The PRISMA guideline was used in this study. Results A total of 17 pre-clinical studies were selected from 7638 studies. 4 studies reported that muscle atrophy and injury harmed memory, functional factors, and neurons in the brain for rodents with or without Alzheimer's disease (AD). 3 studies observed exercise induced muscle to secrete factors, including lactate, fibronectin type III domain-containing protein 5 (FNDC5), and cathepsin B, which plays essential roles in the elevation of cognitive functions and brain-derived neurotrophic factor (BDNF) levels. Muscle-targeted treatments including electrical stimulation and intramuscular injections had effective remote effects on the hippocampus. 6 studies showed that muscle-specific overexpression of scFv59 and Neprilysin, or myostatin knockdown alleviated AD symptoms. 1 study showed that muscle insulin resistance also led to deficient hippocampal neurogenesis in MKR mice. Conclusions The skeletal muscle is involved in the mediation of cognitive function. The evidence was established by the response in the brain (altered number of neurons, functional factors, and other AD pathological characteristics) with muscle atrophy or injury, muscle secretory factors, and muscle-targeted treatments. The translational potential of this paper This study summarizes the current evidence in how muscle affects cognition in molecular levels, which supports muscle-specific treatments as potential clinical strategies to prevent cognitive dysfunction.
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Affiliation(s)
- Chaoran Liu
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Pui Yan Wong
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Simon Kwoon Ho Chow
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Wing Hoi Cheung
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ronald Man Yeung Wong
- Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
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42
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Salinas-Rodríguez A, Palazuelos-González R, Gonzalez-Bautista E, Manrique-Espinoza B. Editorial: Sarcopenia, Cognitive Function, and the Heterogeneity in Aging. J Nutr Health Aging 2023; 27:240-242. [PMID: 37170429 DOI: 10.1007/s12603-023-1910-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Affiliation(s)
- A Salinas-Rodríguez
- Betty Manrique-Espinoza, Center for Evaluation and Surveys Research, National Institute of Public Health, Av. Universidad #655. Colonia Santa María Ahuacatitlan, ZC 62100 Cuernavaca, Mexico. Phone: +52 (777) 3293900,
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43
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Chen LK. Editorial: Aging, Body Composition, and Cognitive Decline: Shared and Unique Characteristics. J Nutr Health Aging 2023; 27:929-931. [PMID: 37997711 DOI: 10.1007/s12603-023-2022-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 11/06/2023] [Indexed: 11/25/2023]
Affiliation(s)
- L-K Chen
- Prof. Liang-Kung Chen, Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, No. 201, Sec 2, Shih-Pai Road, Taipei, Taiwan, TEL: +886-2-28757830, Fax: +886-2-28757711,
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44
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Verrall CE, Tran DL, Yang JYM, Lubans DR, Winlaw DS, Ayer J, Celermajer D, Cordina R. Exercise as therapy for neurodevelopmental and cognitive dysfunction in people with a Fontan circulation: A narrative review. Front Pediatr 2023; 11:1111785. [PMID: 36861078 PMCID: PMC9969110 DOI: 10.3389/fped.2023.1111785] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/25/2023] [Indexed: 02/15/2023] Open
Abstract
People with a Fontan circulation are at risk of neurodevelopmental delay and disability, and cognitive dysfunction, that has significant implications for academic and occupational attainment, psychosocial functioning, and overall quality of life. Interventions for improving these outcomes are lacking. This review article discusses current intervention practices and explores the evidence supporting exercise as a potential intervention for improving cognitive functioning in people living with a Fontan circulation. Proposed pathophysiological mechanisms underpinning these associations are discussed in the context of Fontan physiology and avenues for future research are recommended.
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Affiliation(s)
- Charlotte Elizabeth Verrall
- Heart Centre for Children, The Children's Hospital at Westmead, Sydney, NSW, Australia.,Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.,Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Derek Lee Tran
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, The University of Sydney School of Medicine, Sydney, NSW, Australia.,Charles Perkins Centre, Heart Research Institute, Sydney, NSW, Australia
| | - Joseph Yuan-Mou Yang
- Developmental Imaging, Murdoch Children's Research Institute, Melbourne, VIC, Australia.,Neuroscience Research, Murdoch Children's Research Institute, Melbourne, VIC, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.,Department of Neurosurgery, Neuroscience Advanced Clinical Imaging Service (NACIS), Royal Children's Hospital, Melbourne, VIC, Australia
| | - David Revalds Lubans
- Centre for Active Living and Learning, College of Human and Social Futures, University of Newcastle, Callaghan, NSW, Australia.,Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.,Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - David Scott Winlaw
- Cardiothoracic Surgery, the Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Julian Ayer
- Heart Centre for Children, The Children's Hospital at Westmead, Sydney, NSW, Australia.,Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - David Celermajer
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, The University of Sydney School of Medicine, Sydney, NSW, Australia.,Charles Perkins Centre, Heart Research Institute, Sydney, NSW, Australia
| | - Rachael Cordina
- Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Central Clinical School, The University of Sydney School of Medicine, Sydney, NSW, Australia.,Charles Perkins Centre, Heart Research Institute, Sydney, NSW, Australia.,Heart Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia
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45
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Malin SK, Stewart NR, Ude AA, Alderman BL. Brain insulin resistance and cognitive function: influence of exercise. J Appl Physiol (1985) 2022; 133:1368-1380. [PMID: 36269295 PMCID: PMC9744647 DOI: 10.1152/japplphysiol.00375.2022] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 12/15/2022] Open
Abstract
Exercise has systemic health benefits in people, in part, through improving whole body insulin sensitivity. The brain is an insulin-sensitive organ that is often underdiscussed relative to skeletal muscle, liver, and adipose tissue. Although brain insulin action may have only subtle impacts on peripheral regulation of systemic glucose homeostasis, it is important for weight regulation as well as mental health. In fact, brain insulin signaling is also involved in processes that support healthy cognition. Furthermore, brain insulin resistance has been associated with age-related declines in memory and executive function as well as Alzheimer's disease pathology. Herein, we provide an overview of brain insulin sensitivity in relation to cognitive function from animal and human studies, with particular emphasis placed on the impact exercise may have on brain insulin sensitivity. Mechanisms discussed include mitochondrial function, brain growth factors, and neurogenesis, which collectively help combat obesity-related metabolic disease and Alzheimer's dementia.
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Affiliation(s)
- Steven K Malin
- Department of Kinesiology & Health, Rutgers University, New Brunswick, New Jersey
- Division of Endocrinology, Metabolism & Nutrition, Rutgers University, New Brunswick, New Jersey
- New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, New Jersey
- Institute of Translational Medicine and Science, Rutgers University, New Brunswick, New Jersey
| | - Nathan R Stewart
- Department of Kinesiology & Health, Rutgers University, New Brunswick, New Jersey
| | - Andrew A Ude
- Department of Kinesiology & Health, Rutgers University, New Brunswick, New Jersey
| | - Brandon L Alderman
- Department of Kinesiology & Health, Rutgers University, New Brunswick, New Jersey
- Center of Alcohol and Substance Use Studies, Rutgers University, New Brunswick, New Jersey
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46
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Maier AB. Sarcopenia is a serious disease and should be taken seriously. ANZ J Surg 2022; 92:3124-3125. [PMID: 36527694 DOI: 10.1111/ans.18154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 10/30/2022] [Indexed: 12/23/2022]
Affiliation(s)
- Andrea B Maier
- Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.,Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore
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47
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Rappe A, McWilliams TG. Mitophagy in the aging nervous system. Front Cell Dev Biol 2022; 10:978142. [PMID: 36303604 PMCID: PMC9593040 DOI: 10.3389/fcell.2022.978142] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 09/07/2022] [Indexed: 02/01/2024] Open
Abstract
Aging is characterised by the progressive accumulation of cellular dysfunction, stress, and inflammation. A large body of evidence implicates mitochondrial dysfunction as a cause or consequence of age-related diseases including metabolic disorders, neuropathies, various forms of cancer and neurodegenerative diseases. Because neurons have high metabolic demands and cannot divide, they are especially vulnerable to mitochondrial dysfunction which promotes cell dysfunction and cytotoxicity. Mitophagy neutralises mitochondrial dysfunction, providing an adaptive quality control strategy that sustains metabolic homeostasis. Mitophagy has been extensively studied as an inducible stress response in cultured cells and short-lived model organisms. In contrast, our understanding of physiological mitophagy in mammalian aging remains extremely limited, particularly in the nervous system. The recent profiling of mitophagy reporter mice has revealed variegated vistas of steady-state mitochondrial destruction across different tissues. The discovery of patients with congenital autophagy deficiency provokes further intrigue into the mechanisms that underpin neural integrity. These dimensions have considerable implications for targeting mitophagy and other degradative pathways in age-related neurological disease.
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Affiliation(s)
- Anna Rappe
- Translational Stem Cell Biology and Metabolism Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Thomas G. McWilliams
- Translational Stem Cell Biology and Metabolism Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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48
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Traylor MK, Bauman AJ, Saiyasit N, Frizell CA, Hill BD, Nelson AR, Keller JL. An examination of the relationship among plasma brain derived neurotropic factor, peripheral vascular function, and body composition with cognition in midlife African Americans/Black individuals. Front Aging Neurosci 2022; 14:980561. [PMID: 36092801 PMCID: PMC9453229 DOI: 10.3389/fnagi.2022.980561] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/08/2022] [Indexed: 11/22/2022] Open
Abstract
African American/Black individuals have been excluded from several lines of prominent neuroscience research, despite exhibiting disproportionately higher risk factors associated with the onset and magnitude of neurodegeneration. Therefore, the objective of the current investigation was to examine potential relationships among brain derived neurotropic factor (BDNF), peripheral vascular function, and body composition with cognition in a sample of midlife, African American/Black individuals. Midlife adults (men: n = 3, 60 ± 4 years; women: n = 9, 58 ± 5 years) were invited to complete two baseline visits separated by 4 weeks. Peripheral vascular function was determined by venous occlusion plethysmography, a dual-energy X-ray absorptiometry was used to determine body composition, and plasma was collected to quantify BDNF levels. The CNS Vital Signs computer-based test was used to provide scores on numerous cognitive domains. The principal results included that complex attention (r = 0.629) and processing speed (r = 0.734) were significantly (p < 0.05) related to the plasma BDNF values. However, there was no significant (p > 0.05) relationship between any vascular measure and any cognitive domain or BDNF value. Secondary findings included the relationship between lean mass and peak hyperemia (r = 0.758) as well as total hyperemia (r = 0.855). The major conclusion derived from these results was that there is rationale for future clinical trials to use interventions targeting increasing BDNF to potentially improve cognition. Additionally, these results strongly suggest that clinicians aiming to improve cognitive health via improvements in the known risk factor of vascular function should consider interventions capable of promoting the size and function of skeletal muscle, especially in the African American/Black population.
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Affiliation(s)
- Miranda K. Traylor
- Integrative Laboratory of Exercise and Applied Physiology (iLEAP), Department of Health, Kinesiology, and Sport, College of Education and Professional Studies, University of South Alabama, Mobile, AL, United States
| | - Allison J. Bauman
- Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, AL, United States
| | - Napatsorn Saiyasit
- Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, AL, United States
| | - Carl A. Frizell
- Physician Assistant Sciences Program, School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, United States
| | - Benjamin D. Hill
- Department of Psychology, College of Arts and Sciences, University of South Alabama, Mobile, AL, United States
| | - Amy R. Nelson
- Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, AL, United States
| | - Joshua L. Keller
- Integrative Laboratory of Exercise and Applied Physiology (iLEAP), Department of Health, Kinesiology, and Sport, College of Education and Professional Studies, University of South Alabama, Mobile, AL, United States
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