Progressive loss of PGC-1alpha expression in aging muscle potentiates glucose intolerance and systemic inflammation

Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.

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Sczelecki S, Besse-Patin A, Abboud A, Kleiner S, Laznik-Bogoslavski D, Wrann CD, Ruas JL, Haibe-Kains B, Estall JL