Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging

Aging is a major risk factor for metabolic disease and loss of skeletal muscle mass and strength, a condition known as sarcopenia. Both conditions present a major health burden to the elderly population. Here, we analyzed the effect of mildly increased PGC-1α expression in skeletal muscle during aging. We found that transgenic MCK-PGC-1α animals had preserved mitochondrial function, neuromuscular junctions, and muscle integrity during aging. Increased PGC-1α levels in skeletal muscle prevented muscle wasting by reducing apoptosis, autophagy, and proteasome degradation. The preservation of muscle integrity and function in MCK-PGC-1α animals resulted in significantly improved whole-body health; both the loss of bone mineral density and the increase of systemic chronic inflammation, observed during normal aging, were prevented. Importantly, MCK-PGC-1α animals also showed improved metabolic responses as evident by increased insulin sensitivity and insulin signaling in aged mice. Our results highlight the importance of intact muscle function and metabolism for whole-body homeostasis and indicate that modulation of PGC-1α levels in skeletal muscle presents an avenue for the prevention and treatment of a group of age-related disorders.