期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 48, 页码 20405-20410出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911570106
关键词
mitochondria; PGC-1 alpha
资金
- Public Health Service [NS041777, CA85700, EY10804, AG0005917, DK61562, DK54477]
- Muscular Dystrophy Association
- Ellison Foundation
- United Mitochondrial Disease Foundation
- NATIONAL CANCER INSTITUTE [R01CA085700] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY010804] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054477, R01DK061562, R56DK054477] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041777, R56NS041777] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG005917] Funding Source: NIH RePORTER
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-1 alpha expression in skeletal muscle during aging. We found that transgenic MCK-PGC-1 alpha animals had preserved mitochondrial function, neuromuscular junctions, and muscle integrity during aging. Increased PGC-1 alpha levels in skeletal muscle prevented muscle wasting by reducing apoptosis, autophagy, and proteasome degradation. The preservation of muscle integrity and function in MCK-PGC-1 alpha 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-1 alpha 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-1 alpha levels in skeletal muscle presents an avenue for the prevention and treatment of a group of age-related disorders.
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