Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men

Clinical Science, Journal Year: 2023, Volume and Issue: 137(22), P. 1721 - 1751

Published: Nov. 1, 2023

Abstract Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic biochemical pathways that collectively influence trajectories susceptibility to pathology in humans. skeletal muscle undergoes profound morphological physiological changes loss strength, mass, function, condition known as sarcopenia. The aetiology sarcopenia whilst research this area growing rapidly, there relative paucity human studies, particularly older women. Here, we evaluate how the nine classic ageing: genomic instability, telomere attrition, epigenetic alterations, proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication contribute pathophysiology We also highlight five novel particular significance inflammation, neural extracellular matrix reduced vascular perfusion, ionic dyshomeostasis, discuss are interconnected. Their clinical relevance translational potential considered.

Language: Английский

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Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 934 - 934

Published: April 15, 2023

Mitochondria are one of the organelles undergoing rapid alteration during senescence process. Senescent cells show an increase in mitochondrial size, which is attributed to accumulation defective mitochondria, causes oxidative stress. Defective mitochondria also targets stress, and vicious cycle between stress contributes onset development aging age-related diseases. Based on findings, strategies reduce have been suggested for effective treatment In this article, we discuss alterations consequent Then, causal role investigated by examining how diseases exacerbated induced Furthermore, assess importance targeting regulation suggest different therapeutic Therefore, review will not only shed light a new perspective but provide through

Language: Английский

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Restoration of epigenetic impairment in the skeletal muscle and chronic inflammation resolution as a therapeutic approach in sarcopenia

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102267 - 102267

Published: March 9, 2024

Language: Английский

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Mitochondrial involvement in sarcopenia

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(3)

Published: Feb. 2, 2024

Abstract Sarcopenia lowers the quality‐of‐life for millions of people across world, as accelerated loss skeletal muscle mass and function contributes to both age‐ disease‐related frailty. Physical activity remains only proven therapy sarcopenia date, but alternatives are much sought after manage this progressive disorder in individuals who unable exercise. Mitochondria have been widely implicated etiology increasingly suggested attractive therapeutic targets help restore perturbed balance between protein synthesis breakdown that underpins atrophy. Reviewing current literature, we note mitochondrial bioenergetic changes generally interpreted intrinsic dysfunction renders cells incapable making sufficient ATP fuel synthesis. Based on reported effects interventions, however, argue observed may instead reflect an adaptation pathologically decreased energy expenditure sarcopenic muscle. Discrimination these mechanistic possibilities will be crucial improving management sarcopenia.

Language: Английский

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Bidirectional transitions of sarcopenia states in older adults: The longitudinal evidence from CHARLS

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(5), P. 1915 - 1929

Published: July 12, 2024

Sarcopenia, the age-related loss of muscle mass and function, brings multiple adverse outcomes including disability death. Several sarcopenia consensuses have newly introduced premorbid concept possible recommended early lifestyle interventions. Bidirectional transitions states been revealed in several chronic diseases yet not clarified sarcopenia. This study aims to investigate underlying transition patterns states.

Language: Английский

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Mitigating disuse‐induced skeletal muscle atrophy in ageing: Resistance exercise as a critical countermeasure

Experimental Physiology, Journal Year: 2024, Volume and Issue: 109(10), P. 1650 - 1662

Published: Aug. 6, 2024

The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due the presence 'anabolic resistance', resulting in loss. Sarcopenia can be transiently but markedly accelerated through periods disuse-induced (i.e., unloading) atrophy reduced physical activity, sickness, immobilisation or hospitalisation. Periods disuse are detrimental older adults' overall quality life and substantially increase their risk falls, social dependence, early mortality. Disuse events induce various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis mitochondrial dysfunction, all which tip scales favour a negative net protein balance subsequent Concerningly, recovery from is more for adults than younger counterparts. Resistance training (RT) potent stimulus that robustly stimulate synthesis mitigate losses when implemented before, during following unloading. RT may take form traditional weightlifting-focused RT, bodyweight lower- higher-load RT. When combined sufficient dietary protein, accelerate event, frailty improve mobility; however, few regularly participate A feasible practical approach improving accessibility acceptability use resistance bands. Moving forward, must prescribed consequences atrophy.

Language: Английский

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The Role of Mitochondria in Mediation of Skeletal Muscle Repair

Muscles, Journal Year: 2023, Volume and Issue: 2(2), P. 119 - 163

Published: March 24, 2023

Musculoskeletal health is directly linked to independence and longevity, but disease aging impairs muscle mass health. Complete repair after a pathological or physiological injury critical for maintaining function, yet compromised disuse, in conditions such as metabolic diseases, cancer, aging. Regeneration of damaged tissue critically dependent upon achieving the optimal function satellite cells (muscle stem cells, MSCs). MSC remodeling highly its microenvironment, MSCs, which on functional capacity their mitochondria. Muscle energy demanding mitochondria provide primary source production during regeneration. However, induce mitochondrial dysfunction, limits Nevertheless, role likely extends beyond ATP could potentially important regulatory signaling MSCs from injury. The scope current research regeneration molecules exosomes, largely with goal understanding ways improve function. This review focuses skeletal myogenesis/regeneration repair. A therapeutic strategy improving number will be discussed means enhancing Highlights: (a). Mitochondrial dysfunction regeneration; (b). cell (MSC) can modulated by mitochondria; (c). Enhancing may an

Language: Английский

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Age-Associated Differences in Recovery from Exercise-Induced Muscle Damage

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 255 - 255

Published: Jan. 30, 2024

Understanding the intricate mechanisms governing cellular response to resistance exercise is paramount for promoting healthy aging. This narrative review explored age-related alterations in recovery from exercise, focusing on nuanced aspects of exercise-induced muscle damage older adults. Due limited number studies adults that attempt delineate age differences discovery, we delve into multifaceted influences chronic low-grade inflammation, modifications extracellular matrix, and role lipid mediators shaping landscape aging skeletal muscle. From our literature search, it evident aged displays delayed, prolonged, inefficient recovery. These changes can be attributed anabolic resistance, stiffening mitochondrial dysfunction, unresolved inflammation as well satellite cell function. Collectively, these impairments may impact subsequent adaptations exercise. Insights gleaned this exploration inform targeted interventions aimed at enhancing efficacy training programs tailored specific needs adults, ultimately fostering preserving functional independence.

Language: Английский

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Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(11)

Published: May 3, 2024

Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels metabolism based on frequency intake, but its mechanisms in sarcopenia unknown. We found that once-weekly intermittent rescued quality aged 24-month-old mice levels comparable young 4-month-old mice. discovered an age- sex-independent receptor transactivation program encompassing PGC1α co-factor Lipin1. Treatment coordinately improved mitochondrial abundance isoform 1 mass 4 myocyte-specific PGC1α, which was required for treatment-driven increase carbon shuttling from glucose amino acid biogenesis. also probed Lipin1 as non-redundant factor coaxing upregulation stimulation oxidative anabolic effects. Our study unveils aging-resistant druggable myocytes sarcopenia.

Language: Английский

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Altered Relaxation and Mitochondria-Endoplasmic Reticulum Contact Sites Precede Major (Mal)adaptations in Aging Skeletal Muscle and are Prevented by Exercise

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in force, sarcopenia is associated with atrophy fast-to-slow fiber type switching, which typically secondary denervation humans rodents. However, very little known about cellular changes preceding these important (mal)adaptations. To this matter, mitochondria the sarcoplasmic reticulum are critical for tension generation myofibers. They physically interact at boundaries of sarcomeres forming subcellular hubs called mitochondria-endo/sarcoplasmic contacts (MERCs). Yet, whether MERCs ultrastructure proteome occur early aging unknown. Here, studying young adult older mice we reveal that slows relaxation leading longer excitation-contraction-relaxation (ECR) cycles before maximal force switching takes place. We MERC mitochondria-associated ER membrane (MAM) protein composition also affected closely rate relaxation. Additionally, demonstrate regular exercise preserves aging. Finally, profile a set MAM proteins involved energy metabolism, quality control, Ca 2+ homeostasis, cytoskeleton integrity redox balance inversely regulated by exercise. These may represent new targets preserve function individuals.

Language: Английский

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