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Functional effects of muscle PGC-1alpha in aged animals.
Skeletal Muscle ( IF 4.9 ) Pub Date : 2020-05-06 , DOI: 10.1186/s13395-020-00231-8
Steven Yang 1 , Emanuele Loro 2 , Shogo Wada 1 , Boa Kim 1 , Wei-Ju Tseng 3 , Kristina Li 1 , Tejvir S Khurana 2 , Zoltan Arany 1
Affiliation  

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.

中文翻译:

肌肉PGC-1alpha对老年动物的功能作用。

PGC-1(过氧化物酶体增殖物激活的受体-γ共激活因子-1)α是有效的转录共激活因子,可协调众多代谢过程的激活。运动会强烈诱导肌肉中PGC-1alpha的表达,而骨骼肌中PGC-1alpha的过度表达会激活线粒体的氧化代谢和新血管形成,从而显着增加耐力。根据这些发现,尽管这些发现引起了争议,但已提出PGC-1alpha可防止与年龄相关的肌肉减少症,骨骼丢失和全身代谢功能障碍。因此,我们全面评估了在骨骼肌中过表达PGC-1alpha的24个月大转基因小鼠的肌肉和全身功能以及新陈代谢。我们发现,PGC-1alpha在促进肌肉氧化能力和防止肌肉易疲劳性方面的强大作用在老年动物中持续存在,尽管以牺牲肌肉力量为代价。但是,骨骼肌PGC-1alpha并不能防止骨质流失,反而会加剧骨质流失,也不会对全身代谢成分或胰岛素敏感性产生长期益处。在骨骼肌中PGC-1alpha过度表达的雄性动物中可见对肌肉减少症的保护,而在雌性动物中则没有。综上所述,PGC-1alpha到老年的肌肉特异性表达对肌肉的易疲劳性具有有益的影响,并可能保护男性免受肌肉减少症的影响,但并不能改善全身代谢,并且似乎会加剧与年龄有关的小梁骨丢失。尽管以牺牲肌肉力量为代价。但是,骨骼肌PGC-1alpha并不能防止骨质流失,反而会加剧骨质流失,也不会对全身代谢成分或胰岛素敏感性产生长期益处。在骨骼肌中PGC-1alpha过度表达的雄性动物中可见对肌肉减少症的保护,而在雌性动物中则没有。综上所述,PGC-1alpha到老年的肌肉特异性表达对肌肉的易疲劳性具有有益的影响,并可能保护男性免受肌肉减少症的影响,但并不能改善全身代谢,并且似乎会加剧与年龄有关的小梁骨丢失。尽管以牺牲肌肉力量为代价。但是,骨骼肌PGC-1alpha并不能防止骨质流失,反而会加剧骨质流失,也不会对全身代谢成分或胰岛素敏感性产生长期益处。在骨骼肌中PGC-1alpha过度表达的雄性动物中可见对肌肉减少症的保护,而在雌性动物中则没有。综上所述,PGC-1alpha到老年的肌肉特异性表达对肌肉的易疲劳性具有有益的影响,并可能保护男性免受肌肉减少症的影响,但并不能改善全身代谢,并且似乎会加剧与年龄有关的小梁骨丢失。在骨骼肌中PGC-1alpha过度表达的雄性动物中可见对肌肉减少症的保护,而在雌性动物中则没有。综上所述,PGC-1alpha到老年的肌肉特异性表达对肌肉的易疲劳性具有有益的影响,并可能保护男性免受肌肉减少症的影响,但并不能改善全身代谢,并且似乎会加剧与年龄有关的小梁骨丢失。在骨骼肌中PGC-1alpha过度表达的雄性动物中可见对肌肉减少症的保护,而在雌性动物中则没有。综上所述,PGC-1alpha到老年的肌肉特异性表达对肌肉的易疲劳性具有有益的影响,并可能保护男性免受肌肉减少症的影响,但并不能改善全身代谢,并且似乎会加剧与年龄有关的小梁骨丢失。
更新日期:2020-05-06
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