{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:30:02Z","timestamp":1789684202771,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T00:00:00Z","timestamp":1512518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcopenia is defined as the age\u2010related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2\u20135% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle\u2010aged controls using both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non\u2010sarcopenic skeletal muscle phenotypes during ageing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, <jats:italic>n<\/jats:italic>\u00a0=\u00a07) or non\u2010sarcopenic (HENS, <jats:italic>n<\/jats:italic>\u00a0=\u00a021) and healthy middle\u2010aged control (HMC, <jats:italic>n<\/jats:italic>\u00a0=\u00a022) groups. An <jats:italic>in vitro<\/jats:italic> system of myogenesis (using myoblasts from human donors aged 17\u201383\u00a0years) was used to mimic the environmental challenges of muscle regeneration over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01, Pax7, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) compared with HMC. Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5 (Myf5) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and the late myogenesis marker myogenin (MyoG) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) were increased in HENS. In addition, there was a 30\u2010fold upregulation of TNF\u2010\u03b1 in HENS compared with HMC (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). The <jats:italic>in vitro<\/jats:italic> system demonstrated age\u2010related upregulation of pro\u2010inflammatory cytokines (2\u2010fold upregulation of interleukin (IL)\u20106, IL\u20108 mRNA, increased secretion of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and IL\u20106, all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) associated with impaired kinetics of myotube differentiation.<\/jats:p><jats:p>The HSE biopsy samples showed satellite cell activation (Pax7, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) compared with HMC. However, no significant upregulation of the early myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker myogenin was upregulated (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><jats:p>Higher activation of the oxidative stress pathway was found in HENS compared with the HSE group. In contrast, there was 10\u2010fold higher upregulation of HSPA1A a stress\u2010induced chaperone acting upon misfolded proteins in HSE compared with the HENS group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative\u2010stress and mis\u2010folded protein response (HSPA1A), may be associated with the development of sarcopenia. The <jats:italic>in vitro<\/jats:italic> system of young and old myoblasts replicated some of the differences between young and old muscle.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12252","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T02:18:49Z","timestamp":1512613129000},"page":"93-105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Alterations in the <i>in vitro<\/i> and <i>in vivo<\/i> regulation of muscle regeneration in healthy ageing and the influence of sarcopenia"],"prefix":"10.1002","volume":"9","author":[{"given":"Joanna","family":"Brzeszczy\u0144ska","sequence":"first","affiliation":[{"name":"Tissue Injury and Repair Group, Centre for Regenerative Medicine University of Edinburgh  Edinburgh UK"},{"name":"Clinical Sciences (Surgery) University of Edinburgh  Edinburgh 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