Increased mitochondrial biogenesis in muscle improves aging phenotypes in the mtDNA mutator mouse. Hum Mol Genet 2012 May 15;21(10):2288-97
Date
02/24/2012Pubmed ID
22357654Pubmed Central ID
PMC3335313DOI
10.1093/hmg/dds049Scopus ID
2-s2.0-84860445228 (requires institutional sign-in at Scopus site) 85 CitationsAbstract
Aging is an intricate process that increases susceptibility to sarcopenia and cardiovascular diseases. The accumulation of mitochondrial DNA (mtDNA) mutations is believed to contribute to mitochondrial dysfunction, potentially shortening lifespan. The mtDNA mutator mouse, a mouse model with a proofreading-deficient mtDNA polymerase γ, was shown to develop a premature aging phenotype, including sarcopenia, cardiomyopathy and decreased lifespan. This phenotype was associated with an accumulation of mtDNA mutations and mitochondrial dysfunction. We found that increased expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a crucial regulator of mitochondrial biogenesis and function, in the muscle of mutator mice increased mitochondrial biogenesis and function and also improved the skeletal muscle and heart phenotypes of the mice. Deep sequencing analysis of their mtDNA showed that the increased mitochondrial biogenesis did not reduce the accumulation of mtDNA mutations but rather caused a small increase. These results indicate that increased muscle PGC-1α expression is able to improve some premature aging phenotypes in the mutator mice without reverting the accumulation of mtDNA mutations.
Author List
Dillon LM, Williams SL, Hida A, Peacock JD, Prolla TA, Lincoln J, Moraes CTAuthor
Joy Lincoln PhD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingAnimals
DNA, Mitochondrial
Mice
Mice, Transgenic
Mitochondria
Muscle, Skeletal
Mutation
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Phenotype
Trans-Activators
Transcription Factors
