PGC-1ss Down-Regulation Is Associated With Reduced ERR Activity and MCAD Expression in Skeletal Muscle of Senescence-Accelerated Mice
Open Access
- 1 August 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journals of Gerontology: Series A
- Vol. 61 (8) , 773-780
- https://doi.org/10.1093/gerona/61.8.773
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.Keywords
This publication has 23 references indexed in Scilit:
- Metabolic control through the PGC-1 family of transcription coactivatorsCell Metabolism, 2005
- PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cellsCardiovascular Research, 2005
- Impaired expression of NADH dehydrogenase subunit 1 and PPARγ coactivator-1 in skeletal muscle of ZDF ratsJournal of Lipid Research, 2004
- Down-Regulation of Acyl-CoA Oxidase Gene Expression in Heart of Troglitazone-Treated Mice through a Mechanism Involving Chicken Ovalbumin Upstream Promoter Transcription Factor IIMolecular Pharmacology, 2003
- Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin ResistanceScience, 2003
- Deactivation of peroxisome proliferator–activated receptor-α during cardiac hypertrophic growthJournal of Clinical Investigation, 2000
- Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1Cell, 1999
- Peroxisome Proliferator-activated Receptor α Activation Modulates Cellular Redox Status, Represses Nuclear Factor-κB Signaling, and Reduces Inflammatory Cytokine Production in AgingJournal of Biological Chemistry, 1998
- A Role for Estrogen-related Receptor α in the Control of Mitochondrial Fatty Acid β-Oxidation during Brown Adipocyte DifferentiationJournal of Biological Chemistry, 1997
- Age-related changes in learning and memory in the senescence-accelerated mouse (SAM)Physiology & Behavior, 1986