The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

► Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. ► We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. ► Treating aged mice with the adipokine leptin significantly increased muscle mass an...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-09, Vol.400 (3), p.379-383
Main Authors: Hamrick, Mark W., Herberg, Samuel, Arounleut, Phonepasong, He, Hong-Zhi, Shiver, Austin, Qi, Rui-Qun, Zhou, Li, Isales, Carlos M., Mi, Qing-Sheng
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Age
AGING
Aging - drug effects
Aging - genetics
Aging - pathology
Animals
ELDERLY PEOPLE
FATS
FIBERS
Gene Expression Profiling
HAZARDS
Leptin - therapeutic use
MASS
MICE
Mice, Inbred C57BL
microRNAs
MicroRNAs - genetics
miR-221
miR-223
miR-31
Muscle Development - drug effects
Muscle Development - genetics
Muscle, Skeletal - drug effects
Muscle, Skeletal - pathology
MUSCLES
Muscular Atrophy - drug therapy
NUTRIENTS
Sarcopenia
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Summary:► Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. ► We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. ► Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. ► Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.08.079