Journal
JOURNAL OF CELL SCIENCE
Volume 118, Issue 20, Pages 4813-4821Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02602
Keywords
muscle; ageing; fibre; myoblast; satellite cell; MyoD
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Funding
- Medical Research Council [G0300213] Funding Source: researchfish
- MRC [G0300213] Funding Source: UKRI
- Medical Research Council [G0300213] Funding Source: Medline
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Skeletal muscle fibres are multinucleate syncitial cells that change size during adult life depending on functional demand. The relative contribution of change in nuclear number and/or cell growth to fibre size change is unclear. We report that nuclei/unit length decreases in larger fibres during skeletal muscle ageing. This leads to an increased size of nuclear domain (quantity of cytoplasm/number of nuclei within that cytoplasm). Initially, larger fibres have more satellite cells than small fibres, but this advantage is lost as satellite cells decline with age. These changes are accompanied by an overall decline in fibre size, returning domain size to the normal range. Exacerbated loss of fibre nuclei per unit length during ageing of myoD-null mice provides the first experimental support for the hypothesis that a satellite cell defect causes inadequate nuclear replacement. We propose a model in which a decline in satellite cell function and/or number during ageing leads to a loss of nuclei from large fibres and an associated domain size increase that triggers cytoplasmic atrophy through the normal cell-size-regulating machinery.
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