Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle
Abstract Age‐related loss of muscle mass and function is underpinned by changes at the myocellular level. However, our understanding of the aged muscle phenotype might be confounded by factors secondary to ageing per se, such as inactivity and adiposity. Here, using healthy, lean, recreationally act...
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Wiley
2025-02-01
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| Series: | Experimental Physiology |
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| Online Access: | https://doi.org/10.1113/EP092222 |
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| author | Oscar Horwath Marcus Moberg Sebastian Edman Andrew Philp William Apró |
| author_facet | Oscar Horwath Marcus Moberg Sebastian Edman Andrew Philp William Apró |
| author_sort | Oscar Horwath |
| collection | DOAJ |
| description | Abstract Age‐related loss of muscle mass and function is underpinned by changes at the myocellular level. However, our understanding of the aged muscle phenotype might be confounded by factors secondary to ageing per se, such as inactivity and adiposity. Here, using healthy, lean, recreationally active, older men, we investigated the impact of ageing on myocellular properties in skeletal muscle. Muscle biopsies were obtained from young men (22 ± 3 years, n = 10) and older men (69 ± 3 years, n = 11) matched for health status, activity level and body mass index. Immunofluorescence was used to assess myofibre composition, morphology (size and shape), capillarization, the content of satellite cells and myonuclei, the spatial relationship between satellite cells and capillaries, denervation and myofibre grouping. Compared with young muscle, aged muscle contained 53% more type I myofibres, in addition to smaller (−32%) and misshapen (3%) type II myofibres (P < 0.05). Aged muscle manifested fewer capillaries (−29%) and satellite cells (−38%) surrounding type II myofibres (P < 0.05); however, the spatial relationship between these two remained intact. The proportion of denervated myofibres was ∼2.6‐fold higher in old than young muscle (P < 0.05). Aged muscle had more grouped type I myofibres (∼18‐fold), primarily driven by increased size of existing groups rather than increased group frequency (P < 0.05). Aged muscle displayed selective deterioration of type II myofibres alongside increased denervation and myofibre grouping. These data are key to understanding the cellular basis of age‐related muscle decline and reveal a pressing need to fine‐tune strategies to preserve type II myofibres and innervation status in ageing populations. |
| format | Article |
| id | doaj-art-4914e5d8cc1f49b0a774361163741198 |
| institution | Kabale University |
| issn | 0958-0670 1469-445X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Experimental Physiology |
| spelling | doaj-art-4914e5d8cc1f49b0a7743611637411982025-01-31T06:19:50ZengWileyExperimental Physiology0958-06701469-445X2025-02-01110227729210.1113/EP092222Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscleOscar Horwath0Marcus Moberg1Sebastian Edman2Andrew Philp3William Apró4Department of Physiology, Nutrition and Biomechanics The Swedish School of Sport and Health Sciences Stockholm SwedenDepartment of Physiology, Nutrition and Biomechanics The Swedish School of Sport and Health Sciences Stockholm SwedenDepartment of Physiology, Nutrition and Biomechanics The Swedish School of Sport and Health Sciences Stockholm SwedenCentre for Healthy Ageing Centenary Institute Sydney NSW AustraliaDepartment of Physiology, Nutrition and Biomechanics The Swedish School of Sport and Health Sciences Stockholm SwedenAbstract Age‐related loss of muscle mass and function is underpinned by changes at the myocellular level. However, our understanding of the aged muscle phenotype might be confounded by factors secondary to ageing per se, such as inactivity and adiposity. Here, using healthy, lean, recreationally active, older men, we investigated the impact of ageing on myocellular properties in skeletal muscle. Muscle biopsies were obtained from young men (22 ± 3 years, n = 10) and older men (69 ± 3 years, n = 11) matched for health status, activity level and body mass index. Immunofluorescence was used to assess myofibre composition, morphology (size and shape), capillarization, the content of satellite cells and myonuclei, the spatial relationship between satellite cells and capillaries, denervation and myofibre grouping. Compared with young muscle, aged muscle contained 53% more type I myofibres, in addition to smaller (−32%) and misshapen (3%) type II myofibres (P < 0.05). Aged muscle manifested fewer capillaries (−29%) and satellite cells (−38%) surrounding type II myofibres (P < 0.05); however, the spatial relationship between these two remained intact. The proportion of denervated myofibres was ∼2.6‐fold higher in old than young muscle (P < 0.05). Aged muscle had more grouped type I myofibres (∼18‐fold), primarily driven by increased size of existing groups rather than increased group frequency (P < 0.05). Aged muscle displayed selective deterioration of type II myofibres alongside increased denervation and myofibre grouping. These data are key to understanding the cellular basis of age‐related muscle decline and reveal a pressing need to fine‐tune strategies to preserve type II myofibres and innervation status in ageing populations.https://doi.org/10.1113/EP092222ageinghuman skeletal muscleNCAMPax7sarcopenia |
| spellingShingle | Oscar Horwath Marcus Moberg Sebastian Edman Andrew Philp William Apró Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle Experimental Physiology ageing human skeletal muscle NCAM Pax7 sarcopenia |
| title | Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| title_full | Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| title_fullStr | Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| title_full_unstemmed | Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| title_short | Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| title_sort | ageing leads to selective type ii myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle |
| topic | ageing human skeletal muscle NCAM Pax7 sarcopenia |
| url | https://doi.org/10.1113/EP092222 |
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