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Transcriptional Activation of PGC‐1α in Skeletal Muscle: Influence of Aging and Exercise
Author(s) -
Carter Heather,
Shuen Michael,
Joseph Rosette,
Hood David
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.826.2
Subject(s) - skeletal muscle , mitochondrial biogenesis , biology , transcription (linguistics) , endocrinology , epigenetics , medicine , gene expression , methyltransferase , dna methylation , mitochondrion , transcription factor , microbiology and biotechnology , gene , methylation , biochemistry , linguistics , philosophy
PGC‐1α is largely responsible for the expression of numerous genes encoding mitochondrial proteins and the maintenance of organelle content and quality. Exercise is a potent stimulus to induce the transcription of PGC‐1α in young, healthy muscle. However, in aging muscle mitochondrial content is compromised, concurrent with declines in PGC‐1α mRNA and protein expression. It is unknown whether a contractile activity (CA) stimulus to aging muscle would induce PGC‐1α transcription in a similar manner as that of young muscle. Thus, the tibialis anterior muscles of 6 and 35 month‐old Fischer 344BN rats were electroporated bilaterally with a 1.5kb PGC‐1α promoter‐luciferase reporter construct. In resting aged muscle, there was a reduction of ~50% in PGC‐1α transcriptional activation compared to the young control. This was accompanied by a greater percentage of methylated DNA in aged muscle, an epigenetic modification which inhibits gene transcription. In addition, protein content of the DNA methyltransferase, DNMT3b, was increased by 1.9‐fold in aged skeletal muscle. In young muscle, PGC‐1α transcription was increased by ~2.5‐fold after CA and a one hour recovery period. However, in aged muscle PGC‐1α transcription was reduced ~7‐fold compared to that observed in the young animals. These results suggest that aged muscle has divergent qualitative and quantitative responses of PGC‐1α transcription compared to that of young animals which may be a consequence of increased DNA methylation. This may account, in part, for the attenuated mitochondrial biogenesis response of aged muscle to contractile activity. Supported by CIHR and NSERC.