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  Somatic mitochondrial DNA mutations in mammalian aging

Larsson, N. (2010). Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem, 79, 683-706. doi:10.1146/annurev-biochem-060408-093701.

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 Creators:
Larsson, N.G.1, Author           
Affiliations:
1Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942286              

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Free keywords: Aging/*physiology Animals DNA, Mitochondrial/*genetics Electron Transport Humans Mitochondria/*genetics/physiology Mutation
 Abstract: Mitochondrial dysfunction is heavily implicated in the multifactorial aging process. Aging humans have increased levels of somatic mtDNA mutations that tend to undergo clonal expansion to cause mosaic respiratory chain deficiency in various tissues, such as heart, brain, skeletal muscle, and gut. Genetic mouse models have shown that somatic mtDNA mutations and cell type-specific respiratory chain dysfunction can cause a variety of phenotypes associated with aging and age-related disease. There is thus strong observational and experimental evidence to implicate somatic mtDNA mutations and mosaic respiratory chain dysfunction in the mammalian aging process. The hypothesis that somatic mtDNA mutations are generated by oxidative damage has not been conclusively proven. Emerging data instead suggest that the inherent error rate of mitochondrial DNA (mtDNA) polymerase gamma (Pol gamma) may be responsible for the majority of somatic mtDNA mutations. The roles for mtDNA damage and replication errors in aging need to be further experimentally addressed.

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 Dates: 2010-03-312010-03-31
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: 20350166
DOI: 10.1146/annurev-biochem-060408-093701
ISSN: 0066-4154
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Title: Annu Rev Biochem
  Alternative Title : Annual review of biochemistry
Source Genre: Journal
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Pages: - Volume / Issue: 79 Sequence Number: - Start / End Page: 683 - 706 Identifier: -