PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle

Abstract

The aim of the present study was to test the hypothesis that exercise training prevents an age-associated decline in skeletal muscle mitochondrial enzymes through a PGC-1α dependent mechanism. Whole body PGC-1α knock-out (KO) and littermate wildtype (WT) mice were submitted to long term running wheel exercise training or a sedentary lifestyle from 2 to 13 month of age. Furthermore, a group of approximately 4-month-old mice was used as young untrained controls. There was in both genotypes an age-associated ∼30% decrease in citrate synthase (CS) activity and superoxide dismutase (SOD)2 protein content in 13-month-old untrained mice compared with young untrained mice. However, training prevented the age-associated decrease in CS activity and SOD2 protein content only in WT mice, but long term exercise training did increase HKII protein content in both genotypes. In addition, while CS activity and protein expression of cytc and SOD2 were 50–150% lower in skeletal muscle of PGC-1α mice than WT mice, the expression of the pro-apoptotic protein Bax and the anti-apoptotic Bcl2 was ∼30% elevated in PGC-1α KO mice. In conclusion, the present findings indicate that PGC-1α is required for training-induced prevention of an age-associated decline in CS activity and SOD2 protein expression in skeletal muscle.