4.8 Article Retracted Publication

被撤回的出版物: Increased muscle PGC-1 alpha expression protects from sarcopenia and metabolic disease during aging(Retracted article. See vol.113,pg.E8502,2016)

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911570106

关键词

mitochondria; PGC-1 alpha

资金

  1. Public Health Service [NS041777, CA85700, EY10804, AG0005917, DK61562, DK54477]
  2. Muscular Dystrophy Association
  3. Ellison Foundation
  4. United Mitochondrial Disease Foundation
  5. NATIONAL CANCER INSTITUTE [R01CA085700] Funding Source: NIH RePORTER
  6. NATIONAL EYE INSTITUTE [R01EY010804] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054477, R01DK061562, R56DK054477] Funding Source: NIH RePORTER
  8. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041777, R56NS041777] Funding Source: NIH RePORTER
  9. NATIONAL INSTITUTE ON AGING [R01AG005917] Funding Source: NIH RePORTER

向作者/读者索取更多资源

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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