Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:773-780 (2006)
© 2006 The Gerontological Society of America

PGC-1ß Down-Regulation Is Associated With Reduced ERR{alpha} Activity and MCAD Expression in Skeletal Muscle of Senescence-Accelerated Mice

Ricardo Rodríguez-Calvo, Mireia Jové, Teresa Coll, Antoni Camins, Rosa M. Sánchez, Marta Alegret, Manuel Merlos, Mercè Pallàs, Juan C. Laguna and Manuel Vázquez-Carrera

Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain.

Address correspondence to Manuel Vázquez-Carrera, PhD, Unitat de Farmacologia, Facultat de Farmàcia, Diagonal 643, E-08028 Barcelona, Spain. E-mail: mvazquezcarrera{at}ub.edu

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-1ß expression (52% reduction, p <.001) was observed compared to the senescence-accelerated resistant mice (SAM-R1). In agreement with the proposed role of PGC-1ß as an estrogen-related receptor (ERR) protein ligand, the expression of the ERR{alpha} 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 ERR{alpha} DNA-binding activity of SAM-P8. These findings indicate that the age-mediated decrease in PGC-1ß expression in SAM-P8 skeletal muscle affects the expression of genes involved in mitochondrial fatty acid oxidation.




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