title: Current understanding of sarcopenia: possible candidates modulating muscle mass.
abstract: The world's elderly population is expanding rapidly, and we are now faced with the significant challenge of maintaining or improving physical activity, independence, and quality of life in the elderly. Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Muscle loss has been linked with several proteolytic systems, including the ubuiquitin-proteasome, lysosome-autophagy, and tumor necrosis factor (TNF)-α/nuclear factor-kappaB (NF-κB) systems. Although many factors are considered to regulate age-dependent muscle loss, this gentle atrophy is not affected by factors known to enhance rapid atrophy (denervation, hindlimb suspension, etc.). In addition, defects in Akt-mammalian target of rapamycin (mTOR) and serum response factor (SRF)-dependent signaling have been found in sarcopenic muscle. Intriguingly, more recent studies indicated an apparent functional defect in autophagy- and myostatin-dependent signaling in sarcopenic muscle. In this review, we summarize the current understanding of the adaptation of many regulators in sarcopenia.
authors.affiliation: Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, 1-1 Hibarigaoka, Tenpaku-cho, Toyohashi, 441-8580, Japan, ksakuma@las.tut.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sakuma
authors.forename: Wataru
authors.initials: W
authors.lastname: Aoi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamaguchi
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D006801:Humans; D055435:Myostatin / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D055435:Myostatin; D026362:Serum Response Factor; D014452:Ubiquitins