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A well\u2010functioning neuromuscular system is fundamental to quality of life and functional independence. The systemic deterioration of tissue and organ function during ageing is reflected in the diverse cellular and molecular mechanisms implicated in the age\u2010related loss of muscle mass and strength and its extreme form, termed sarcopenia. Proposed contributors include neurodegeneration, impaired proteostasis, deficient regeneration, systemic hormonal decline, chronic inflammation, and dysregulation of muscle\u2010resident cell populations such as muscle stem cells, fibro\u2010adipogenic progenitors and immune cells. Recent efforts have added granularity to our understanding of the molecular response of muscle to ageing and started to unravel the cellular origins of these signals. Advancements in cell\u2010targeting strategies (e.g. AAV capsids and antibody\u2010targeted therapeutics) are opening new avenues for targeted interventions. Nonetheless, this raises the salient question \u2013 what should treatments for age\u2010related muscle wasting target? While anabolic and catabolic signalling within muscle fibres has been the primary target of strategies to counteract age\u2010related muscle loss, these efforts may be futile if impairment in other cell types such as muscle stem cells and motor neurons drive the wasting process. Furthermore, individual differences in activity, nutrition, sex, comorbidities and genetics are likely to influence the predominant mechanisms driving age\u2010related muscle wasting. This multifactorial condition may therefore require a multifactorial solution, with scientists focusing on diverse causal mechanisms to identify and develop effective interventions.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70446-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp289838","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:09:42Z","timestamp":1773666582000},"page":"7059-7075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treating age\u2010related loss of muscle mass and function: Where should we be focusing?"],"prefix":"10.1113","volume":"604","author":[{"given":"Daniel J.","family":"Ham","sequence":"first","affiliation":[{"name":"Biozentrum \u2013 Center for Molecular Life Sciences University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Fry","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avnika Ashok","family":"Ruparelia","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research Department of Anatomy and Physiology University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Anatomy and Physiology School of Biomedical Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne  Melbourne Victoria Australia"},{"name":"Australian Regenerative Medicine Institute Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyuan T.","family":"Ngo","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Motor Neuron Disease Research University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Institute for Bioengineering and Nanotechnology University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Lamon","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition School of Exercise and Nutrition Sciences Deakin University Geelong Victoria 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