Role of Myostatin Signaling in Aging: Applications for Age-Related Sarcopenia

Author(s): Hilary A. Wilkinson.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 10 , Issue 4 , 2010

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Abstract:

Myostatin is a member of the TGFbeta family which is known to promote muscle wasting. Reduction of function mutations in this signaling molecule results in increased muscle mass in many different species examined including mice and humans. Age-related sarcopenia results in loss of strength and is a major contributing factor to falls and loss of independence in the elderly. Studies in rodents have demonstrated a decrease in myostatin expression in skeletal muscle whereas in humans there appears to be an increase in myostatin expression with age. Myostatin knockout mice have been reported to be resistant to the development of age-related sarcopenia and in humans, myostatin polymorphisms have been correlated with changes in muscle mass in the elderly. Treatment with an inhibitory antibody to myostatin increases muscle mass and, in combination with exercise, improves physical performance and metabolic parameters in aged mice and inhibition of myostatin pathway signaling with a dominant negative protein in aged mice speeds muscle regeneration after injury. Studies in old mice and rats suggest inhibition or loss of myostatin improves key features of skeletal muscle organization which are compromised in age-related sarcopenia and understanding the role of myostatin in aging skeletal muscle may reveal potential novel therapies for this unmet medical need.

Keywords: Myostatin, aging, sarcopenia, TGFbeta, muscle, myofiber, motor neuron, TGF, GH, IGF-1, total body fat, Skeletal muscle, oxidative stress, mRNA, glycolytic fibers, hypertrophy, Genetic, Genomic, BrdU, WHASII, K153R, K153R allele, ACVR2B, PF-354, PCNA, immunoreactive, Testosterone, myoanabolic, FDA, mmobilization

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Article Details

VOLUME: 10
ISSUE: 4
Year: 2010
Page: [211 - 216]
Pages: 6
DOI: 10.2174/187152210793663801
Price: $58

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