Abstract This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-g coactivator-1α (PGC-1α) mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1a also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.
Significant point: PGC-1α has been identified as a master regulator of a wide range of cellular functions and gene expression. This review summaries its critical role in skeletal muscle in terms of energy metabolism, antioxidant homeostasis, and inflammation, ultimately affecting muscle health and aging.