{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:21:49Z","timestamp":1790727709487,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>This study aimed to determine which physiological factors impact net efficiency (\u03b7net) in oldest\u2010old individuals at different stages of skeletal muscle disuse. To this aim, we examined \u03b7net, central haemodynamics, peripheral circulation, and peripheral factors (skeletal muscle fibre type, capillarization and concentration of mitochondrial DNA [mtDNA]). Twelve young (YG; 25 \u00b1 2 years), 12 oldest\u2010old mobile (OM; 87 \u00b1 3 years), and 12 oldest\u2010old immobile (OI; 88 \u00b1 4 years) subjects performed dynamic knee extensor (KE) and elbow flexors (EF) exercise. Pulmonary oxygen uptake, photoplethysmography, Doppler ultrasound and muscle biopsies of the vastus lateralis and biceps brachii were used to assess central and peripheral adaptations to advanced ageing and disuse. Compared to the YG (12.1 \u00b1 2.4%), the \u03b7net of lower\u2010limb muscle was higher in the OM (17.6 \u00b1 3.5%, <jats:italic>P<\/jats:italic> &lt; 0.001), and lower in the OI (8.9 \u00b1 1.9%, <jats:italic>P<\/jats:italic> &lt; 0.001). These changes in \u03b7net during KE were coupled with significant peripheral adaptations, revealing strong correlations between \u03b7net and the proportion of type I muscle fibres (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.82), as well as [mtDNA] (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.77). No differences in \u03b7net were evident in the upper\u2010limb muscles between YG, OM and OI. In view of the differences in limb\u2010specific activity across the lifespan, these findings suggest that \u03b7net is reduced by skeletal muscle inactivity and not by chronological age, <jats:italic>per se<\/jats:italic>. Likewise, this study revealed that the age\u2010related changes in \u03b7net are not a consequence of central or peripheral haemodynamic adaptations, but are likely a product of peripheral changes related to skeletal muscle fibre type and mitochondrial density.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15894-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Although the effects of ageing and muscle disuse deeply impact the cardiovascular and skeletal muscle function, the combination of these factors on the mechanical efficiency are still a matter of debate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>By measuring both upper\u2010 and lower\u2010limb muscle function, which experience differing levels of disuse, we examined the influence of central and peripheral haemodynamics, and skeletal muscle factors linked to mechanical efficiency.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Across the ages and degree of disuse, upper\u2010limb muscles exhibited a preserved work economy. In the legs the oldest\u2010old without mobility limitations exhibited an augmented mechanical efficiency, which was reduced in those with an impairment in ambulation. These changes in mechanical efficiency were associated with the proportion of type I muscle fibres.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Recognition that the mechanical efficiency is not simply age\u2010dependent, but the consequence of inactivity and subsequent skeletal muscle changes, highlights the importance of maintaining physical activity across the lifespan.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285639","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T21:31:13Z","timestamp":1704231073000},"page":"355-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Physiological determinants of mechanical efficiency during advanced ageing and disuse"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2469-8787","authenticated-orcid":false,"given":"Massimo","family":"Venturelli","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett R.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"The Murtha Cancer Center at Walter Reed Bethesda  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cantor","family":"Tarperi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Naro","sequence":"additional","affiliation":[{"name":"DAHFMO Unit of Histology and Medical Embryology Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-361X","authenticated-orcid":false,"given":"Carlo","family":"Reggiani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Donato","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"The Murtha Cancer Center at Walter Reed Bethesda  Bethesda Maryland USA"},{"name":"George E. 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