Molecular mechanisms and therapeutics of the deficit in specific force in ageing skeletal muscle.
The age-related impairment in muscle force is only partially explained by the loss of muscle mass. The loss both in specific and absolute forces contributes to the muscle weakness measured in the elderly and in animal models of ageing. Successful interventions aimed at preventing age-associated functional deficits will require a better insight into the mechanisms underlying the decline in muscle-specific force. The present review article is focused on recent evidence supporting excitation-contraction uncoupling as a key factor underlying fast and slow muscle fiber impairment with ageing. The molecular, functional and structural factors supporting this theory and counteracting measures such as insulin-like growth factor 1 transgenic overexpression are discussed.
Delbono
Osvaldo
O
Department of Physiology and Pharmacology, Department of Internal Medicine, Gerontology and Neuroscience Program, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. odelbono@wfubmc.edu
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D007334:Insulin-Like Growth Factor I; D002118:Calcium