期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2018, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2018/8561892
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类别
资金
- Agencia Nacional de Promocion Cientifica y Tecnologica (FONCyT) [PICT 02418]
- Universidad de Buenos Aires [UBACyT 20020130100574BA]
Programmed and damage aging theories have traditionally been conceived as stand-alone schools of thought. However, the p66(Shc) adaptor protein has demonstrated that aging-regulating genes and reactive oxygen species (ROS) are closely interconnected, since its absence modifies metabolic homeostasis by providing oxidative stress resistance and promoting longevity. p66(Shc(-/-)) mice are a unique opportunity to further comprehend the bidirectional relationship between redox homeostasis and the imbalance of mitochondrial biogenesis and dynamics during aging. This study shows that brain mitochondria of p66(Shc(-/-)) aged mice exhibit a reduced alteration of redox balance with a decrease in both ROS generation and its detoxification activity. We also demonstrate a strong link between reactive nitrogen species (RNS) and mitochondrial function, morphology, and biogenesis, where low levels of ONOO- formation present in aged p66(Shc(-/-)) mouse brain prevent protein nitration, delaying the loss of biological functions characteristic of the aging process. Sirt3 modulates age-associated mitochondrial biology and function via lysine deacetylation of target proteins, and we show that its regulation depends on its nitration status and is benefited by the improved NAD(+)/NADH ratio in aged p66(Shc(-/-)) brain mitochondria. Low levels of protein nitration and acetylation could cause the metabolic homeostasis maintenance observed during aging in this group, thus increasing its lifespan.
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