Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging(Retracted article. See vol.113,pg.E8502,2016)
Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging(Retracted article. See vol.113,pg.E8502,2016)
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DOI：
10.1073/pnas.0911570106
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发表时间：
2009-12-01
影响因子：
11.1
通讯作者：
Moraes, Carlos T.
中科院分区：
文献类型：
--
作者：
Wenz, Tina;Rossi, Susana G.;Moraes, Carlos T.
衰老是代谢性疾病和骨骼肌质量和强度损失的主要风险因素，这种情况称为肌肉减少症。这两种疾病都给老年人带来了沉重的健康负担。在这里，我们分析了在衰老过程中骨骼肌中PGC-1 α表达轻度增加的影响。我们发现转基因MCK-PGC-1 alpha动物在衰老过程中保留了线粒体功能，神经肌肉接头和肌肉完整性。骨骼肌中增加的PGC-1 α水平通过减少细胞凋亡、自噬和蛋白酶体降解来防止肌肉萎缩。MCK-PGC-1 α动物肌肉完整性和功能的保留导致全身健康显著改善;在正常衰老期间观察到的骨矿物质密度损失和全身慢性炎症增加都得到了预防。重要的是，MCK-PGC-1 α动物还显示出改善的代谢反应，这通过老年小鼠中胰岛素敏感性和胰岛素信号传导的增加而得到证实。我们的研究结果强调了完整肌肉功能和代谢对全身稳态的重要性，并表明骨骼肌中PGC-1 α水平的调节为预防和治疗一组年龄相关疾病提供了一种途径。
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.