Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism
Article first published online: 17 SEP 2013
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 1, pages 80–91, February 2014
How to Cite
Akasaki, Y., Ouchi, N., Izumiya, Y., Bernardo, B. L., LeBrasseur, N. K. and Walsh, K. (2014), Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism. Aging Cell, 13: 80–91. doi: 10.1111/acel.12153
- Issue published online: 16 JAN 2014
- Article first published online: 17 SEP 2013
- Accepted manuscript online: 23 AUG 2013 09:07AM EST
- Manuscript Accepted: 8 AUG 2013
- Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad
- Japanese Society for the Promotion of Science Kakenhi Grant-in-Aid. Grant Number: 24890178
- NIH. Grant Numbers: AG034972, HL068758, HL081587
- Mayo Clinic
- adipose tissue;
- type IIb muscle
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.