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Functional effects of muscle PGC-1alpha in aged animals

机译：肌肉PGC-1Alpha在老年动物中的功能效应

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PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of numerous metabolic processes. Exercise strongly induces PGC-1alpha expression in muscle, and overexpression of PGC-1alpha in skeletal muscle activates mitochondrial oxidative metabolism and neovascularization, leading to markedly increased endurance. In light of these findings, PGC-1alpha has been proposed to protect from age-associated sarcopenia, bone loss, and whole-body metabolic dysfunction, although these findings have been controversial. We therefore comprehensively evaluated muscle and whole-body function and metabolism in 24-month-old transgenic mice that over-express PGC-1alpha in skeletal muscle. We find that the powerful effects of PGC-1alpha on promoting muscle oxidative capacity and protection from muscle fatigability persist in aged animals, although at the expense of muscle strength. However, skeletal muscle PGC-1alpha does not prevent bone loss and in fact accentuates it, nor does it have long-term benefit on whole-body metabolic composition or insulin sensitivity. Protection from sarcopenia is seen in male animals with overexpression of PGC-1alpha in skeletal muscle but not in female animals. In summary, muscle-specific expression of PGC-1alpha into old age has beneficial effects on muscle fatigability and may protect from sarcopenia in males, but does not improve whole-body metabolism and appears to worsen age-related trabecular bone loss.
机译：PGC-1（过氧化物酶体 - 增殖器 - 活化受体-γCaCtivator-1）α是一种有效的转录共同诱导剂，其协调许多代谢过程的活化。运动强烈诱导肌肉中的PGC-1αα表达，并且在骨骼肌中的PGC-1α的过度表达激活线粒体氧化代谢和新生血管形成，导致耐久性显着增加。鉴于这些发现，已经提出了PGC-1Alpha以保护来自年龄相关的肌肉病毒，骨丢失和全身代谢功能障碍，尽管这些发现是有争议的。因此，我们在骨骼肌中过于表达PGC-1α的24个月常转基因小鼠中综合评估了肌肉和全身功能和新陈代谢。我们发现PGC-1Alpha对促进肌肉氧化能力和免受肌肉疲劳性的保护的强大效果持续在老年动物中，尽管以肌肉力量为代价。然而，骨骼肌PGC-1Alpha不会防止骨质损失，实际上突出，它也没有对全身代谢组成或胰岛素敏感性的长期益处。在骨骼肌肉中具有过表达的雄性动物的雄性动物中可以看出Sarcopenia，但在骨骼肌中的过表达，但不在女性动物中。总之，PGC-1Alpha的肌肉特异性表达为旧时期对肌肉疲劳性具有有益的影响，并且可以保护肌肉疲劳性，但不会改善全身代谢，似乎恶化的年龄相关的小梁骨质损失。

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