PGC-1β down-regulation is associated with reduced ERRα activity and MCAD expression in skeletal muscle of senescence-accelerated mice

Mitochondrial dysfunction is involved in the development of aging. Here, we examined the effect of aging on the skeletal muscle expression of two isoforms of the transcriptional peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator-1 (PGC-1) in an experimental murine model of accelerated aging, the senescence-accelerated mouse (SAM). The senescence-accelerated prone mice (SAM-P8) showed no changes in PGC-1 alpha, but a decrease in PGC-1 beta expression (52% reduction, p < .001) was observed compared to the senescence-accelerated resistant mice (SAM-R1). In agreement with the proposed role of PGC-1 beta as an estrogen-related receptor (ERR) protein ligand, the expression of the ERR alpha target gene medium-chain acylcoenzyme A dehydrogenase was strongly suppressed (85%, p < .001) in SAM-P8. The decrease in the expression of medium-chain acyl-coenzyme A dehydrogenase was consistent with the reduction in ERR alpha DNA-binding activity of SAM-P8. These findings indicate that the age-mediated decrease in PGG-1 beta expression in SAM-P8 skeletal muscle affects the expression of genes involved in mitochondrial fatty acid oxidation.