The clinical impact and biological mechanisms of skeletal muscle aging

Abstract

Skeletal muscle is a highly plastic tissue that remarkably adapts to diverse stimuli including exercise, injury, disuse, and, as discussed here, aging. Humans achieve peak skeletal muscle mass and strength in mid-life and then experience a progressive decline of up to 50% by the ninth decade. The loss of muscle mass and function with aging is a phenomenon termed sarcopenia. It is evidenced by the loss and atrophy of muscle fibers and the concomitant accretion of fat and fibrous tissue. Sarcopenia has been recognized as a key driver of limitations in physical function and mobility, but is perhaps less appreciated for its role in age-related metabolic dysfunction and loss of organismal resilience. Similar to other tissues, muscle is prone to multiple forms of age-related molecular and cellular damage, including disrupted protein turnover, impaired regenerative capacity, cellular senescence, and mitochondrial dysfunction. The objective of this review is to highlight the clinical consequences of skeletal muscle aging, and provide insights into potential biological mechanisms. In light of population aging, strategies to improve muscle health in older adults promise to have a profound public health impact.

Keywords: Autophagy; Exercise; Mitochondria; Physical function; Sarcopenia; Senescence; Strength.

Figure 1.. Age-related changes in skeletal muscle.

The considerable loss of muscle mass and volume with advancing age is attributed to both the loss and atrophy of muscle fibers. The progressive decrease in functional contractile tissue is matched with the accretion of fat and fibrotic tissue. These alterations, along with progressive loss of innervating motor neurons and capillaries, contribute to the age-related loss of muscle strength, power, and endurance.

Figure 2.. Skeletal muscle in health, aging and disease.

Skeletal muscle uniquely generates force and power for diverse forms of physical function, including mobility. It is also a critical metabolic organ that is responsible for the storage of glucose, the oxidation of fatty acids, and is a rich source of amino acids. Based on its size and metabolic activity during both rest and movement, muscle strongly influences both resting energy expenditure (REE) and activity associated energy expenditure (REE). Measures of muscle performance, physical function, and mass are also determinants of physical resilience, the capacity to resist and recover from diverse challenges.