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However, the disconnect between lifespan and \u2018health span\u2019 (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.<\/jats:p>","DOI":"10.1042\/cs20231197","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T05:51:20Z","timestamp":1720763480000},"page":"863-882","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Skeletal muscle dysfunction with advancing age"],"prefix":"10.1042","volume":"138","author":[{"given":"Pardeep","family":"Pabla","sequence":"first","affiliation":[{"name":"1Centre of Metabolism, Ageing and Physiology (COMAP), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor\u00a0J.","family":"Jones","sequence":"additional","affiliation":[{"name":"1Centre of Metabolism, Ageing and Physiology (COMAP), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Piasecki","sequence":"additional","affiliation":[{"name":"1Centre of Metabolism, Ageing and Physiology (COMAP), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, U.K."},{"name":"2MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR), U.K."},{"name":"3NIHR Nottingham Biomedical Research Centre (BRC), U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1430-1870","authenticated-orcid":false,"given":"Bethan\u00a0E.","family":"Phillips","sequence":"additional","affiliation":[{"name":"1Centre of Metabolism, Ageing and Physiology (COMAP), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, U.K."},{"name":"2MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR), U.K."},{"name":"3NIHR Nottingham Biomedical Research Centre (BRC), U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"2024071209510859300_B1","article-title":"Past and projected period and cohort life tables: 2020-based, UK, 1981 to 2070","author":"Office for National Statistics","year":"2022"},{"key":"2024071209510859300_B2","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1152\/physrev.00037.2021","article-title":"Multisystem physiological perspective of human frailty and its modulation by physical activity","volume":"103","author":"Taylor","year":"2023","journal-title":"Physiol. 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