title: Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism.
abstract: 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.
authors.affiliation: Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, 02118, USA; Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Akasaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Bernardo
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Lebrasseur
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019076:Transgenes
chemical_list: D045930:Anabolic Agents; D036341:Intercellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: adipose tissue; diabetes; exercise; mTOR; sarcopenia; type IIb muscle
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