The objective was to elucidate the molecular mechanisms through which exercise confers anti-aging effects and mitigates degenerative functional decline by restoring mitochondrial homeostasis.
Abstract
Summary Age-associated organ dysfunction markedly impairs quality of life and increases mortality in older adults. Aging frequently results in compromised mitochondrial function in organs with high energy demands, such as skeletal muscle, the brain, heart, kidneys, and liver. This impairment leads to excessive production of reactive oxygen species, increased inflammation, energy deficits, and aberrant cellular signaling, collectively fostering cellular senescence, and chronic diseases. Empirical research has demonstrated that regular physical exercise preserves mitochondrial integrity. This review summarizes common and specific responses to exercise in mitochondrial regulation across various organs and provides a comprehensive cross-organ analysis. The objective was to elucidate the molecular mechanisms through which exercise confers anti-aging effects and mitigates degenerative functional decline by restoring mitochondrial homeostasis. This review provides a theoretical foundation for developing targeted anti-aging interventions and for attenuating aging in multiple organs through lifestyle modifications.
Simple Summary Skeletal muscle, the body’s largest metabolic organ, relies critically on mitochondrial integrity for proper function. Mitochondrial quality control encompasses biogenesis, repair, and clearance mechanisms that preserve organelle homeostasis. Dysfunction in these pathways, arising from aging, malnutrition, or disease, precipitates muscle atrophy, impaired bioenergetics, and metabolic dysfunction. This review elucidates the molecular mechanisms governing mitochondrial quality control in skeletal muscle and examines the consequences of its failure. Notably, exercise emerges as a potent, cost-effective intervention to restore mitochondrial homeostasis. Strategic exercise prescription represents a promising approach to sustain musculoskeletal health throughout the lifespan, warranting further investigation into optimal dosing for diverse populations.
This review proposes that tailored exercise strategies targeting mitophagy may provide a scalable, non‐pharmacological approach to preserve mitochondrial quality and functional resilience during aging.
Peng Ran, Li-Fang Yang· IUBMB Life - A Journal of th...· 0 citations
Ageing is a major risk factor for degenerative diseases, including sarcopenia, which is characterized by a progressive loss of skeletal muscle mass and function, frailty, and is associated with increased mortality. Skeletal muscle regeneration relies on muscle stem cells and efficient communication with cellular microenvironment. With ageing, skeletal muscle regenerative capacity declines, and sarcopenia results from complex, multitissue dysregulation involving mitochondrial dysfunction, immune ageing, chronic inflammation, senescence, extracellular matrix modification, disruption of neuromuscular junctions and muscle‐specific vulnerability. This review summarizes current knowledge contributing to sarcopenia and inefficient muscle repair during ageing from cell‐autonomous metabolic dysregulation to age‐associated changes in the local and systemic cellular environment. We also explore recent insights into important role of exercise on muscle tissue health. Overall, emerging technologies, including human muscle atlases and spatial transcriptomics, together with exercise‐based interventions, will help to identify of novel biomarkers and therapeutic targets to better prevent and treat sarcopenia.
J. D. Hernández-Camacho, Marielle Saclier· Journal of Cellular Physiolo...· 0 citations
Sarcopenia is an age-related progressive degenerative disorder of skeletal muscle characterized by declining muscle mass, strength, and function. Increasing evidence indicates that chronic low-grade inflammation plays an important contributory role in its pathogenesis. The inflammatory microenvironment contributes to sarcopenia through complex interactions involving cellular senescence, mitochondrial dysfunction, and sustained inflammatory signaling, forming a self-reinforcing pathological cycle within skeletal muscle. This review synthesizes current evidence on the molecular mechanisms underlying inflammation-driven sarcopenia, with particular emphasis on how inflammatory signaling disrupts protein turnover and satellite cell metabolism. In addition, exercise is examined as a precision "hormone-like" intervention tailored to different sarcopenia phenotypes, highlighting the distinct mechanisms through which resistance training, aerobic exercise, and combined training modulate the senescence-associated phenotype and inflammatory responses. The review further evaluates anti-inflammatory therapeutic strategies, including nutritional interventions, pharmacotherapy, and acupuncture. These approaches improve muscle health by restoring immune balance, enhancing mitochondrial function, modulating the gut-muscle axis, reducing oxidative stress, and promoting the clearance of senescent cells. Finally, emerging precision medicine frameworks and multi-omics strategies that may support individualized sarcopenia management are discussed. Overall, this review provides an integrated perspective on inflammatory signaling in sarcopenia and outlines potential therapeutic strategies targeting the inflammatory microenvironment, offering insights for future research and clinical management.
Xuesong Wang, Shannah Erasmus, Zewen Chu et al.· Aging and Disease· 0 citations
The molecular assembly, physiological roles, and longevity implications of SC in healthy mammals, and emerging evidence supporting SC modulation as a potential strategy for promoting healthy aging are discussed.
Shinichiro Suzuki, K. Ikeda, Toshihiko Takeiwa et al.· Frontiers in Aging· 0 citations
Meloxicam (Mcam) is identified as a small molecule inducer of Cdon that enhances myogenic differentiation, increases muscle mass and function in young mice and mitigates age-related muscle atrophy, and is identified as a potential therapeutic target for age-associated skeletal muscle degeneration.
Ju-Hyeon Bae, Hyun-Kyung So, Yideul Jeong et al.· Experimental and Molecular M...· 0 citations
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