| First Author | Gill JF | Year | 2019 |
| Journal | Aging Cell | Volume | 18 |
| Issue | 5 | Pages | e12993 |
| PubMed ID | 31290266 | Mgi Jnum | J:297012 |
| Mgi Id | MGI:6468863 | Doi | 10.1111/acel.12993 |
| Citation | Gill JF, et al. (2019) Peroxisome proliferator-activated receptor gamma coactivator 1alpha regulates mitochondrial calcium homeostasis, sarcoplasmic reticulum stress, and cell death to mitigate skeletal muscle aging. Aging Cell 18(5):e12993 |
| abstractText | Age-related impairment of muscle function severely affects the health of an increasing elderly population. While causality and the underlying mechanisms remain poorly understood, exercise is an efficient intervention to blunt these aging effects. We thus investigated the role of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), a potent regulator of mitochondrial function and exercise adaptation, in skeletal muscle during aging. We demonstrate that PGC-1alpha overexpression improves mitochondrial dynamics and calcium buffering in an estrogen-related receptor alpha-dependent manner. Moreover, we show that sarcoplasmic reticulum stress is attenuated by PGC-1alpha. As a result, PGC-1alpha prevents tubular aggregate formation and cell death pathway activation in old muscle. Similarly, the pro-apoptotic effects of ceramide and thapsigargin were blunted by PGC-1alpha in muscle cells. Accordingly, mice with muscle-specific gain-of-function and loss-of-function of PGC-1alpha exhibit a delayed and premature aging phenotype, respectively. Together, our data reveal a key protective effect of PGC-1alpha on muscle function and overall health span in aging. |
