Age-related DNA methylation changes: Potential impact on skeletal muscle aging in humans

Human aging is accompanied by a decline in muscle mass and muscle function, which is commonly referred to as sarcopenia. Sarcopenia is associated with detrimental clinical outcomes, such as a reduced quality of life, frailty, an increased risk of falls, fractures, hospitalization, and mortality. The exact underlying mechanisms of sarcopenia are poorly delineated and the molecular mechanisms driving the development and progression of this disorder remain to be uncovered. Previous studies have described age-related differences in gene expression, with one study identifying an age-specific expression signature of sarcopenia, but little is known about the influence of epigenetics, and specially of DNA methylation, in its pathogenesis. In this review, we will focus on the available knowledge in literature on the characterization of DNA methylation profiles during skeletal muscle aging and the possible impact of physical activity and nutrition. We will consider the possible use of the recently developed DNA methylation-based biomarkers of aging called epigenetic clocks in the assessment of physical performance in older individuals. Finally, we will discuss limitations and future directions of this field.