PGC-1α affects aging-related changes in muscle and motor function by modulating specific exercise-mediated changes in old mice.
PGC-1α affects aging-related changes in muscle and motor function by modulating specific exercise-mediated changes in old mice.
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DOI：
10.1111/acel.12697
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发表时间：
2018-03
期刊：
影响因子：
7.8
通讯作者：
Handschin C
中科院分区：
文献类型：
--
作者：
Gill JF;Santos G;Schnyder S;Handschin C
与年龄相关的肌肉功能损伤导致老年人的运动协调性和活动性急剧下降。定期的身体活动是预防和治疗这种年龄相关性退化的唯一有效干预措施。然而，在这种情况下，运动治疗效果的机制仍不清楚。我们评估了老年人的耐力运动训练是否足以影响肌肉和运动功能。此外，由于肌肉过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）是耐力运动适应的关键调节中心，在老年肌肉中表达减少，因此我们研究了PGC-1α参与衰老运动的治疗作用。有趣的是，PGC-1α肌肉特异性敲除和过表达分别促进和减轻了老年小鼠中与衰老相关的肌肉功能恶化的特定方面，而其他肌肉功能障碍在PGC-1α调节后保持不变。令人惊讶的是，我们发现肌肉PGC-1α不仅参与改善肌肉耐力和线粒体重塑，而且还通过有助于维持老年动物的平衡和运动协调来模拟老年耐力运动训练。因此，我们的数据表明，即使在老年进行运动，运动的益处也超出了骨骼肌，并且至少部分由PGC-1α介导。
The age‐related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age‐associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) is a key regulatory hub in endurance exercise adaptation with decreased expression in old muscle, we studied the involvement of PGC‐1α in the therapeutic effect of exercise in aging. Intriguingly, PGC‐1α muscle‐specific knockout and overexpression, respectively, precipitated and alleviated specific aspects of aging‐related deterioration of muscle function in old mice, while other muscle dysfunctions remained unchanged upon PGC‐1α modulation. Surprisingly, we discovered that muscle PGC‐1α was not only involved in improving muscle endurance and mitochondrial remodeling, but also phenocopied endurance exercise training in advanced age by contributing to maintaining balance and motor coordination in old animals. Our data therefore suggest that the benefits of exercise, even when performed at old age, extend beyond skeletal muscle and are at least in part mediated by PGC‐1α.
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影响因子：
3.9
作者：
Leick, Lotte;Lyngby, Stine Secher;Pilegaard, Henriette
通讯作者：
Pilegaard, Henriette
影响因子：
7.7
作者：
Ghosh S;Lertwattanarak R;Lefort N;Molina-Carrion M;Joya-Galeana J;Bowen BP;Garduno-Garcia Jde J;Abdul-Ghani M;Richardson A;DeFronzo RA;Mandarino L;Van Remmen H;Musi N
通讯作者：
Musi N
影响因子：
4.8
作者：
Gouspillou, Gilles;Sgarioto, Nicolas;Hepple, Russell T.
通讯作者：
Hepple, Russell T.
DOI：
10.1111/j.1532-5415.1991.tb03574.x
发表时间：
1991-12-01
影响因子：
6.3
作者：
LORD, SR;CLARK, RD;WEBSTER, IW
通讯作者：
WEBSTER, IW
影响因子：
10.5
作者：
Handschin, Christoph;Kobayashi, Yvonne M.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.