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

Abstract:

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 γ (PPARγ) 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-1α, but a decrease in PGC-1β expression (52% reduction, p < .001) was observed compared to the senescence-accelerated resistant mice (SAM-R1). In agreement with the proposed role of PGC-1β as an estrogen-related receptor (ERR) protein ligand, the expression of the ERRα target gene medium-chain acyl-coenzyme 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 ERRα DNA-binding activity of SAM-P8. These findings indicate that the age-mediated decrease in PGC-1β expression in SAM-P8 skeletal muscle affects the expression of genes involved in mitochondrial fatty acid oxidation. Copyright 2006 by The Gerontological Society of America.