Overexpression of PGC-1α in aging muscle enhances a large sub-set of young-like gene expression patterns

PGC-1α is a transcriptional co-activator known as the master regulator of mitochondrial biogenesis. Its control of gene expression has been suggested to play a role in neurodegenerative diseases and the aging process. We have aged mice overexpressing PGC-1α in skeletal muscle to determine whether life span was altered and whether the transcriptional changes reflect a pattern of expression observed in younger muscle. We found that PGC-1a overexpression had a mild effect on longevity extending maximal survival by approximately 10%. Analyses of muscles protein steady-state levels showed that Pax7 and several autophagy markers levels were markedly increased. MF20 positive myosin heavy chain was markedly reduced, a pattern resembling muscle from young mice. RNAseq showed that several genes overexpressed in the aged-pGC-1α transgenic are expressed at higher levels in young when compared to aged skeletal muscle. As expected, there was increased expression of genes associated with energy metabolism but also of unexpected functional groups