Point Mutations Are Causing Progeroid Phenotypes in the mtDNA Mutator Mouse
نویسندگان
چکیده
منابع مشابه
Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?
Recent studies have demonstrated that transgenic mice with an increased rate of somatic point mutations in mitochondrial DNA (mtDNA mutator mice) display a premature aging phenotype reminiscent of human aging. These results are widely interpreted as implying that mtDNA mutations may be a central mechanism in mammalian aging. However, the levels of mutations in the mutator mice typically are mor...
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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 ...
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Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs) and PPAR γ coactivator-1α (PGC-1α) pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA) mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of prema...
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A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Ep...
متن کاملThe mtDNA mutator mouse: Dissecting mitochondrial involvement in aging
The role of mtDNA mutations in aging has been intensely debated because of their low abundance and correlative connection with aging. The creation of mtDNA mutator mice provided the first evidence that somatic mtDNA mutations have the capacity to cause a variety of aging phenotypes in mammals, and they do so without inducing ROS production or increasing oxidative stress. We have recently provid...
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ژورنال
عنوان ژورنال: Cell Metabolism
سال: 2010
ISSN: 1550-4131
DOI: 10.1016/j.cmet.2009.12.001