Mechanisms of Ageing and Development最新文献_第3页

Aging of the Colon – A Mechanistic View 结肠的衰老——一个机械的观点

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.mad.2025.112143

Christopher Hofmann , Hartmut Geiger

{"title":"Aging of the Colon – A Mechanistic View","authors":"Christopher Hofmann , Hartmut Geiger","doi":"10.1016/j.mad.2025.112143","DOIUrl":"10.1016/j.mad.2025.112143","url":null,"abstract":"<div><div>The colon is one of the gastrointestinal organs most profoundly affected by aging. Recent advances in our understanding of both colonic physiology and the general mechanisms of aging have significantly expanded our knowledge of the types and underlying processes of colonic aging. In this review, we summarize current insights into the cellular and molecular mechanisms that drive physiological aging of the human colon. We examine the unique structural and functional features of key components of the colon, including the epithelium, local immune system, microbiome, enteric neurons, and smooth muscle cells, and explore how aging affects each of these cell populations, ultimately impacting overall colonic function. In the epithelium, increased mutational burden does not appear to be the primary driver of age-related dysfunction. Instead, dysregulation of signaling pathways such as EGF and Wnt is likely responsible for key phenotypic changes. Aged colonic neurons display protein misfolding and axonal dysfunction reminiscent of aging processes observed in the central nervous system. Similarly, smooth muscle cells exhibit impaired contractility, which is associated with disruptions in calcium homeostasis and deficits in cholinergic signaling. At the same time, age-related activation of the local immune system mirrors broader immunosenescence and may be further influenced by shifts in the gut microbiome, although a consistent aging-associated microbiome signature has yet to be identified. These multifaceted changes, combined with the colon’s inherent regional and cellular complexity and the challenges of modeling human colonic aging, continue to fascinate but also pose substantial obstacles for research. Emerging experimental models and clinical strategies offer promising avenues for improving the prevention and treatment of age-associated colonic dysfunction.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112143"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ashwagandha withanolides, Withaferin-A, and Withanone for natural interventions in aging and obesity Ashwagandha Withanolides， Withaferin-A和Withanone对衰老和肥胖的自然干预。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-11-20 DOI: 10.1016/j.mad.2025.112126

Ren Yoshitomi , Rajeswari Nanda , Kazumi Hirano , Sunil C. Kaul , Jaspreet Kaur Dhanjal , Renu Wadhwa

{"title":"Ashwagandha withanolides, Withaferin-A, and Withanone for natural interventions in aging and obesity","authors":"Ren Yoshitomi , Rajeswari Nanda , Kazumi Hirano , Sunil C. Kaul , Jaspreet Kaur Dhanjal , Renu Wadhwa","doi":"10.1016/j.mad.2025.112126","DOIUrl":"10.1016/j.mad.2025.112126","url":null,"abstract":"<div><div>Aging and obesity are closely connected, with obesity being a major risk factor for many age-related diseases caused by chronic inflammation and mobility problems. Lifestyle choices such as good nutrition, including medicinal herbs, and exercise are believed to influence body weight. Ashwagandha, an Ayurvedic adaptogen containing bioactive withanolides, is known to reduce stress, fight cancer, and improve energy metabolism. Its effects on lipid metabolism and obesity remain unclear. CARF (Collaborator of ARF), a protein involved in stress response and cancer regulation, was recently found to control liver lipid metabolism. We used a hepatocyte-based screening assay in which induction of fatty acid accumulation caused downregulation of CARF. On the other hand, cells treated with Ashwagandha withanolides showed CARF recovery and reduction in lipid accumulation. Molecular analyses on key regulators of stress and lipogenesis pathways supported antioxidative and antisteatotic effects of Withaferin-A (Wi-A) and Withanone (Wi-N). We discuss various antiaging activities of Ashwagandha withanolides and report computational molecular modeling-based insights into the interactions of Wi-A and Wi-N with three key targets (Fatty Acid Synthase, FASN; Sterol Regulatory Element-Binding protein-1c, SREBP-1c; and Peroxisome Proliferator-Activated Receptor, PPARγ) of the lipogenesis pathway, highlighting their potential in regulating lipid metabolism and obesity.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112126"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

lncRNA EPB41L4A-AS1: A promising therapeutic target for aging and age-related diseases lncRNA EPB41L4A-AS1：一个有希望的治疗衰老和年龄相关疾病的靶点

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.mad.2025.112118

Minghui Li , Tianzi Li , Xufei Zhang , Kun Li , Ziqiang Wang

{"title":"lncRNA EPB41L4A-AS1: A promising therapeutic target for aging and age-related diseases","authors":"Minghui Li , Tianzi Li , Xufei Zhang , Kun Li , Ziqiang Wang","doi":"10.1016/j.mad.2025.112118","DOIUrl":"10.1016/j.mad.2025.112118","url":null,"abstract":"<div><div>Aging is a natural biological process characterized by progressive cellular and functional decline, significantly increasing susceptibility to age-related diseases. Long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators of cellular processes implicated in aging and age-related diseases. Among these, lncRNA erythrocyte membrane protein band 4.1 like 4 A antisense RNA 1 (EPB41L4A-AS1) has emerged as a key player with significant dysregulation across diverse age-related diseases including cancer, Alzheimer's disease (AD), and type 2 diabetes mellitus (T2DM). This review synthesizes current evidence showing that EPB41L4A-AS1 functions primarily as a tumor suppressor in many cancers, regulates neuronal autophagy and energy metabolism in AD, and modulates inflammatory and metabolic pathways in T2DM. Mechanistically, EPB41L4A-AS1 exerts its effects—via miRNA sponging, regulating key signaling pathways (NF-κB, Rho/ROCK), influencing histone modifications, and modulating cellular metabolism (glycolysis, glutaminolysis, NAD+/ATP synthesis). The compelling evidence positions EPB41L4A-AS1 as a promising, multi-faceted therapeutic target for mitigating the burden of age-related diseases.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112118"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disentangling tau, glymphatic dysfunction and astrocytic activation in amyloid-positive Alzheimer's disease 淀粉样蛋白阳性阿尔茨海默病中Tau蛋白、淋巴功能障碍和星形细胞激活的分离。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1016/j.mad.2025.112113

Hsin-I. Chang , Shih-Wen Chen , Shu-Hua Huang , Shih-Wei Hsu , Chen-Chang Lee , Chung-Guei Huang , Chi-Wei Huang , Chiung-Chih Chang

{"title":"Disentangling tau, glymphatic dysfunction and astrocytic activation in amyloid-positive Alzheimer's disease","authors":"Hsin-I. Chang , Shih-Wen Chen , Shu-Hua Huang , Shih-Wei Hsu , Chen-Chang Lee , Chung-Guei Huang , Chi-Wei Huang , Chiung-Chih Chang","doi":"10.1016/j.mad.2025.112113","DOIUrl":"10.1016/j.mad.2025.112113","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) features tau pathology, neurodegeneration, and cognitive decline. Dysfunction of the glymphatic system, which clears pathological proteins, and astrocytic activation may exacerbate neurodegeneration. We investigated the interplay among tau accumulation, glymphatic dysfunction, and astrocytic activation in amyloid PET-positive AD patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) as a glymphatic biomarker. Our cohort comprised 157 AD patients and 117 cognitively unimpaired controls. We measured DTI-ALPS, plasma GFAP, hippocampal volume, and cognitive scores at two time points. [F18]Florzolotau PET quantified tau burden. Regression analyses assessed associations between biomarkers and cognitive decline, and mediation analysis tested GFAP’s role in tau-driven neurodegeneration. We also compared topographical distributions of DTI-ALPS and GFAP using tau PET and gray matter images. Tau burden emerged as the strongest predictor of cognitive decline, while DTI-ALPS showed no significant cognitive association. GFAP mediated the link between tau burden and hippocampal atrophy, implicating astrocytic activation in tau-driven neurodegeneration. Regional analyses revealed GFAP associations in anterior cingulate and medial temporal areas, contrasting with DTI-ALPS patterns in parasagittal and lateral prefrontal regions. These findings underscore tau burden as the driver of cognitive decline, with astrocytic activation mediating neurodegeneration; glymphatic dysfunction minimally impacts cognition.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112113"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating mitokines GDF-15 and FGF21 are associated with frailty, sarcopenia, and malnutrition in older adults: Evidence from the FRASNET study 循环分裂因子GDF-15和FGF21与老年人虚弱、肌肉减少症和营养不良有关：来自FRASNET研究的证据

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-11-11 DOI: 10.1016/j.mad.2025.112124

Sarah Damanti , Clara Sciorati , Rebecca De Lorenzo , Amanda Avola , Maria Pia Ruggiero , Simona Santoro , Eleonora Senini , Marco Messina , Francesca Farina , Costanza Festorazzi , Giulia Pata , Martina Laffranchi , Martina Mallus , Elena Brioni , Lorena Citterio , Laura Zagato , Marco Simonini , Chiara Lanzani , Paolo Manunta , Angelo A. Manfredi , Patrizia Rovere-Querini

{"title":"Circulating mitokines GDF-15 and FGF21 are associated with frailty, sarcopenia, and malnutrition in older adults: Evidence from the FRASNET study","authors":"Sarah Damanti , Clara Sciorati , Rebecca De Lorenzo , Amanda Avola , Maria Pia Ruggiero , Simona Santoro , Eleonora Senini , Marco Messina , Francesca Farina , Costanza Festorazzi , Giulia Pata , Martina Laffranchi , Martina Mallus , Elena Brioni , Lorena Citterio , Laura Zagato , Marco Simonini , Chiara Lanzani , Paolo Manunta , Angelo A. Manfredi , Patrizia Rovere-Querini","doi":"10.1016/j.mad.2025.112124","DOIUrl":"10.1016/j.mad.2025.112124","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondria-derived GDF15 and FGF21, known as mitokines, are emerging biomarkers of metabolic stress and aging-related decline. Their roles in energy balance, inflammation, and muscle metabolism suggest potential for predicting geriatric syndromes, yet prospective evidence is limited.</div></div><div><h3>Methods</h3><div>Plasma GDF15 and FGF21 and multidimensional geriatric assessment at baseline and at 6-year follow-up in 52 community-dwelling adults aged ≥ 65 years from the FRASNET cohort.</div></div><div><h3>Results</h3><div>Over a six-year follow-up, participants exhibited signs of functional decline, including increased waist circumference, greater fatigue severity, and higher medication use. FGF21 levels declined significantly over time (p = 0.03), whereas GDF15 levels remained stable. Higher baseline GDF15 levels identified individuals at higher risk to become frail (AUC= 0.85 with Fried Phenotype and AUC= 0.96 with Clinical Frailty Scale) or malnourished (AUC=0.94) and at risk to fall (AUC=0.98). FGF21 associated to malnutrition (AUC=0.98). GDF15 prospectively associated to high risk of frailty and negatively associated with physical performance and nutritional status after six years.</div></div><div><h3>Conclusions</h3><div>In this cohort, higher baseline levels of GDF15 and FGF21 were associated with the risk to become frail or malnourished. These findings support the integration of mitokines into early risk stratification tools for older adults. Further validation in larger cohorts is warranted.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112124"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Morin enhances healthspan and neuroprotection in Caenorhabditis elegans via mitochondrial stress adaptation 马桑素通过线粒体应激适应增强秀丽隐杆线虫的健康和神经保护作用。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.mad.2025.112120

Yong-Ha Jo , Hyun-Ok Song , Dong-Sung Lee , Jeong Hoon Cho

{"title":"Morin enhances healthspan and neuroprotection in Caenorhabditis elegans via mitochondrial stress adaptation","authors":"Yong-Ha Jo , Hyun-Ok Song , Dong-Sung Lee , Jeong Hoon Cho","doi":"10.1016/j.mad.2025.112120","DOIUrl":"10.1016/j.mad.2025.112120","url":null,"abstract":"<div><div>Morin, a dietary flavonoid with antioxidant and metabolic activity, promotes healthy ageing in <em>Caenorhabditis elegans</em>. Morin extended lifespan by ∼18 % and alleviated age-related decline in neuronal integrity, locomotion, learning and memory, and intestinal fat accumulation. Mitochondrial potential was moderately decreased, suggesting mild uncoupler–like activity. Morin downregulated <em>daf-2</em> and upregulated <em>daf-16</em>, accompanied by enhanced DAF-16::GFP nuclear localization, indicative of IIS/FOXO pathway activation. Gene expression profiling revealed modulation of mitochondrial stress–responsive (<em>atfs-1</em>, <em>fmo-2</em>), antioxidant (<em>gst-4</em>, <em>hsf-1</em>), and lipid metabolism (<em>fat-6</em>, <em>fat-7</em>) genes. Notably, <em>pink-1</em> and <em>pdr-1</em> expression increased, whereas morin’s neuroprotective effects were abolished in <em>pink-1; pdr-1</em> mutants, suggesting that its benefits may involve PINK-1/PDR-1–dependent mitophagy or mitochondrial quality control. Collectively, morin enhances stress resilience and mitochondrial homeostasis through IIS/FOXO-associated regulation, supporting its potential as a natural compound that promotes healthspan.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112120"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical data-driven classification of pre-frailty reveals sex-specific patterns – Data from the Berlin Aging Study II (BASE-II) 临床数据驱动的虚弱前分类揭示了性别特异性模式——来自柏林老龄化研究II （BASE-II）的数据

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-24 DOI: 10.1016/j.mad.2025.112114

Jeff Didier , Sébastien De Landtsheer , Maria Pires Pacheco , Ali Kishk , Jochen G. Schneider , David Goldeck , Graham Pawelec , Dominik Spira , Ilja Demuth , Thomas Sauter

{"title":"Clinical data-driven classification of pre-frailty reveals sex-specific patterns – Data from the Berlin Aging Study II (BASE-II)","authors":"Jeff Didier , Sébastien De Landtsheer , Maria Pires Pacheco , Ali Kishk , Jochen G. Schneider , David Goldeck , Graham Pawelec , Dominik Spira , Ilja Demuth , Thomas Sauter","doi":"10.1016/j.mad.2025.112114","DOIUrl":"10.1016/j.mad.2025.112114","url":null,"abstract":"<div><div>Frailty is a geriatric condition with multidimensional consequences that strongly affect older adults’ quality of life. The lack of a universal standard to describe, diagnose, and treat frailty further complicates this situation. Nowadays, multitudinous frailty assessment tools are applied depending on the regional and clinical context, adding complexity by increasing heterogeneity in the definition and characterization of frailty. Better insights into the causes and pathophysiology of frailty and its early stages are required to establish strong and accurately tailored treatment rationales for frail patients. We analysed participants aged 60 and above using cross-sectional biochemical and survey data from the Berlin Aging Study II (BASE-II, N = 1512, pre-frail=470, frail=14), applying machine-learning techniques to investigate determinants of physical frailty measured by Fried et al.’s 5-item frailty phenotype. Our findings highlight new prognostic sex-specific biomarkers of pre-frailty (the early stage of frailty) with possible clinical applications, enriching the current sex-agnostic diagnostic scores with easy monitorable physical and physiological characteristics. Low appendicular lean mass and high fat composition in men, or vitamin D deficiency and high white blood cell counts in women, emerged as strong indicators of the respective pre-frailty profiles. Because the number of fully frail individuals was extremely small (n = 14, <1 %), our findings should be interpreted as reflecting predictors of pre-frailty, not of frailty itself. We conclude that understanding the development of frailty remains a complex challenge, and that sex-specific differences must be considered by clinical geriatricians and researchers.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112114"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of concern: Regulation of β-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. 关注表达：散发性阿尔茨海默病模型系统——胆固醇喂养家兔大脑中β-淀粉样蛋白水平的调节。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.mad.2025.112121

R P Jaya Prasanthi, Eric Schommer, Sarah Thomasson, Alex Thompson, Gwen Feist, Othman Ghribi

引用次数: 0

Linking nutrition and aging: A cross-domain analysis of Mediterranean Diet Adhesion Screener components 链接营养和衰老：地中海饮食粘连筛选组件的跨域分析。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.mad.2025.112119

Fatma Hastaoǧlu , Sonia de Pascual-Teresa

{"title":"Linking nutrition and aging: A cross-domain analysis of Mediterranean Diet Adhesion Screener components","authors":"Fatma Hastaoǧlu , Sonia de Pascual-Teresa","doi":"10.1016/j.mad.2025.112119","DOIUrl":"10.1016/j.mad.2025.112119","url":null,"abstract":"<div><div>This study explores the scientific landscape linking the Mediterranean Diet Adherence Screener (MEDAS) to aging-related health outcomes through a comprehensive bibliometric and scoping review approach. Given the increasing prevalence of chronic conditions in aging populations, diet has emerged as a modifiable factor with potential to enhance health span. The Mediterranean diet, characterized by high intake of vegetables, fruits, olive oil, and legumes, has shown promise in promoting cardiovascular, neurological, and metabolic health. MEDAS, a validated 14-item questionnaire developed within the PREDIMED study, serves as a practical tool to assess adherence to this dietary pattern. The current analysis spans literature from 2000 to 2025 and includes 203 peer-reviewed publications indexed in Web of Science. Using VOSviewer and CiteSpace software, co-occurrence maps, keyword clusters, and disease associations were visualized. Results indicate that fish, vegetables, nuts, and olive oil are the most frequently studied MEDAS components. Cardiovascular aging emerged as the most researched domain, followed by general aging and neurodegenerative conditions, while dermatological aging remains underexplored. Key themes such as cognitive decline, frailty, inflammaging, and longevity underscore the multidimensional role of MEDAS. Findings suggest that MEDAS is not only a dietary adherence measure but also a valuable instrument in preventive geriatric nutrition. Its global adaptability, simplicity, and strong predictive value make it a suitable tool for clinical and community-based nutritional strategies. This study contributes a consolidated foundation for future interdisciplinary efforts to integrate diet-based approaches into aging research and public health policy.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112119"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defective mitochondrial quality control in the aging of skeletal muscle 骨骼肌老化过程中线粒体质量控制缺陷。

IF 5.1 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI: 10.1016/j.mad.2025.112112

Emanuele Marzetti , Riccardo Calvani , Helio José Coelho-Junior , Francesco Landi , Anna Picca

{"title":"Defective mitochondrial quality control in the aging of skeletal muscle","authors":"Emanuele Marzetti , Riccardo Calvani , Helio José Coelho-Junior , Francesco Landi , Anna Picca","doi":"10.1016/j.mad.2025.112112","DOIUrl":"10.1016/j.mad.2025.112112","url":null,"abstract":"<div><div>Age-related skeletal muscle decline is a major contributor to frailty, functional impairment, and loss of independence in advanced age. This process is characterized by selective atrophy of type II fibers, impaired excitation–contraction coupling, and reduced regenerative capacity. Emerging evidence implicates mitochondrial dysfunction as a central mechanism in the disruption of muscle homeostasis with age. Beyond ATP production, mitochondria orchestrate redox signaling, calcium handling, and apoptotic pathways, which are increasingly compromised in aged muscle due to chronic oxidative stress and defective quality control. High-resolution respirometry has revealed intrinsic, lifestyle-independent declines in mitochondrial respiratory capacity, while large-scale phenotyping and transcriptomic profiling have established robust associations between mitochondrial integrity, physical performance, and mobility. These findings have prompted a paradigm shift from static descriptions of mitochondrial decline toward dynamic analyses of mitochondrial signaling networks and stress adaptability. Several quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy, and vesicle trafficking, emerge as critical regulators of myocyte integrity. Understanding how these systems deteriorate with age will be pivotal for developing therapeutic targets to preserve muscle function, mitigate sarcopenia, and extend health span.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"228 ","pages":"Article 112112"},"PeriodicalIF":5.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0