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

Authors

  • Yuichi Akasaki,

    1. Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA
    2. Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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  • Noriyuki Ouchi,

    1. Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA
    2. Department of Molecular Cardiology, Nagoya University School of Medicine, Nagoya, Japan
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  • Yasuhiro Izumiya,

    1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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  • Barbara L. Bernardo,

    1. Pfizer Global Research and Development, Groton, CT, USA
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  • Nathan K. LeBrasseur,

    1. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
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  • Kenneth Walsh

    Corresponding author
    1. Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA
    • Correspondence

      Kenneth Walsh, PhD, Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. Tel.: +617 414 2390; fax: +617 414 2391; e-mail: kxwalsh@bu.edu

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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.

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