Glycolytic fast‐twitch muscle fiber restoration counters adverse age‐related changes in body composition and metabolism

Aging Cell

Yuichi Akasaki⁴  Noriyuki Ouchi⁴  Yasuhiro Izumiya³  Barbara L. Bernardo¹  Nathan K. LeBrasseur² 

[1] Pfizer Global Research and Development, Groton, CT, USA;Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA;Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA

关键词: adipose tissue;    diabetes;    exercise;    mTOR;    sarcopenia;    type IIb muscle;   

DOI  :  10.1111/acel.12153

来源: Wiley

【 摘 要 】

Summary

Aging is associated with the development of insulin resistance, increased adiposity, and accumulation of ectopic lipid deposits in tissues and organs. Starting in mid-life there is a progressive decline in lean muscle mass associated with the preferential loss of glycolytic, fast-twitch myofibers. However, it is not known to what extent muscle loss and metabolic dysfunction are causally related or whether they are independent epiphenomena of the aging process. Here, we utilized a skeletal-muscle-specific, conditional transgenic mouse expressing a constitutively active form of Akt1 to examine the consequences of glycolytic, fast-twitch muscle growth in young vs. middle-aged animals fed standard low-fat chow diets. Activation of the Akt1 transgene led to selective skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon aging. The Akt1-mediated increase in muscle mass led to reductions in fat mass and hepatic steatosis in older animals, and corrected age-associated impairments in glucose metabolism. These results indicate that the loss of lean muscle mass is a significant contributor to the development of age-related metabolic dysfunction and that interventions that preserve or restore fast/glycolytic muscle may delay the onset of metabolic disease.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.