Oxidative stress causes DNA damage

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2010

Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction.
Someya S, et al.
«Caloric restriction (CR) extends the life span and health span of a variety of species and slows the progression of age-related hearing loss (AHL), a common age-related disorder associated with oxidative stress. Here, we report that CR reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type mice but fails to modify these phenotypes in mice lacking the mitochondrial deacetylase Sirt3, a member of the sirtuin family. In response to CR, Sirt3 directly deacetylates and activates mitochondrial isocitrate dehydrogenase 2 (Idh2), leading to increased NADPH levels and an increased ratio of reduced-to-oxidized glutathione in mitochondria. In cultured cell, overexpression of Sirt3 and/or Idh2 increases NADPH levels and protects from oxidative stress-induced cell death. Therefore, our findings identify Sirt3 as an essential player in enhancing the mitochondrial glutathione antioxidant defense system during CR and suggest that Sirt3-dependent mitochondrial adaptations may be a central mechanism of aging retardation in mammals.»
#Aging, Animals, Antioxidants, DNA Damage, Female, Glutathione, Hearing Loss, Inbred C57BL, Isocitrate Dehydrogenase, Male, Mice, Mitochondria, Sirtuin 3more...
ncbi.nlm.nih.gov/pubmed/21094524
10.1016/j.cell.2010.10.002

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