It has been identified that skeletal muscle is an endocrine tissue. Since skeletal muscle aging affects not only to muscle strength and function but to systemic aging and lifespan, myokines secreted from skeletal muscle may be crucial factors for intertissue communication during aging. In the present study, we investigated the expression of myokines associated with skeletal muscle aging in taurine transporter knockout (TauTKO) mice, which exhibit the accelerated skeletal muscle aging. Among transforming growth factor (TGF)-beta family genes, only growth and differentiation factor 15 (GDF15) was markedly higher (>3-fold) in skeletal muscle of old TauTKO mice compared with that of either young TauTKO mice or old wild-type mice. Circulating levels of GDF15 were also elevated in old TauTKO mice. An elevation in circulating GDF15 was also observed in very old (30-month-old) wild-type mice, while skeletal GDF15 levels were normal. The treatment of cultured mouse C2C12 myotubular cells with aging-related factors that mediate cellular stresses, such as oxidative stress (hydrogen peroxide) and endoplasmic reticulum stress (tunicamycin and thapsigargin), leads to an increase in GDF15 secretion. In conclusion, GDF15 is a myokine secreted by agingrelated stress and may control aging phenotype.Key words growth differentiation factor 15 (GDF15); sarcopenia; aging cell; skeletal muscle; myokine Aging-related loss of muscle mass and strength causes physical activities of daily living and decreases the QOL.1) Additionally, it has been demonstrated that skeletal muscle mass and strength are well associated with the mortality rate and aging-related diseases in human.2-4) Moreover, several studies in mammals and fruit flies demonstrated that stress-sensing in skeletal muscle influences systemic aging and lifespan, 4) suggesting that non-autonomous communication between aged skeletal muscle and whole body may play a key role in aging process. Skeletal muscle is an endocrine organ that produce cytokines and growth factors, which is called as myokines. 5)
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