Age-associated loss of muscle mass, or
sarcopenia, contributes directly to
frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived
hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific
miRNAs. Aging altered the expression of 57
miRNAs in mouse skeletal muscle, and many of these
miRNAs are now reported to be associated specifically with age-related
muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant
leptin, to determine whether
leptin therapy could improve muscle mass and alter the
miRNA expression profile of aging skeletal muscle.
Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37
miRNAs was altered in muscles of
leptin-treated mice. In particular,
leptin treatment increased the expression of miR-31 and miR-223,
miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific
miRNAs, and that nutrient-related
hormones such as
leptin may be able to reverse
muscle atrophy and alter the expression of
atrophy-related
miRNAs in aging skeletal muscle.