Skeletal muscle weakness in old age: underlying mechanisms

Abstract

Maintenance of muscle mass and strength contributes to mobility which impacts on quality of life. Although muscle atrophy, declining strength, and physical frailty are generally accepted as inevitable concomitants of aging, the causes are unknown. Clarification of the mechanisms responsible for these changes would enhance our understanding of the degree to which they are preventable or treatable. The decline in muscle function between maturity and old age is similar for muscles of many different animals including human beings, and is typified by the decreases of approximately 35% in maximum force, approximately 30% in maximum power, and 20% in normalized force (kN.m-2) and power (W.kg-1) of extensor digitorum longus (EDL) muscles in old compared with adult mice. Much of the age-associated muscle atrophy and declining strength may be explained by motor unit remodeling which appears to occur by selective denervation of muscle fibers with reinnervation by axonal sprouting from an adjacent innervated unit. Muscles in old mice appear more susceptible to injury than muscles in young or adult mice and have a decreased capacity for recovery. The process of age-related denervation may be aggravated by an increased susceptibility of muscles in old animals to contraction-induced injury coupled with impaired capacity for regeneration.