Glycolytic fast‐twitch muscle fiber restoration counters adverse age‐related changes in body composition and metabolism
Open Access
- 17 September 2013
- journal article
- Published by Wiley in Aging Cell
- Vol. 13 (1), 80-91
- https://doi.org/10.1111/acel.12153
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.This publication has 40 references indexed in Scilit:
- Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restrictionProceedings of the National Academy of Sciences of the United States of America, 2012
- Metabolic benefits of resistance training and fast glycolytic skeletal muscleAmerican Journal of Physiology-Endocrinology and Metabolism, 2011
- Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin SensitivityCell Metabolism, 2010
- Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during agingProceedings of the National Academy of Sciences of the United States of America, 2009
- Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolismProceedings of the National Academy of Sciences of the United States of America, 2008
- High-fat diets cause insulin resistance despite an increase in muscle mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese MiceCell Metabolism, 2008
- Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophyJournal of Applied Physiology, 2006
- Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failureJCI Insight, 2005
- Changes in Muscle Morphology, Electromyographic Activity, and Force Production Characteristics During Progressive Strength Training in Young and Older MenThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 1998