Theorizing on Sirt3 and Longevity Mechanisms
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This research group proposes that Sirt3 acts on longevity through increasing antioxidants - we should all be appropriately skeptical, given the very mixed evidence for links between cellular antioxidants and longevity. That said, Sirt3 is located in the mitochondria, and the demonstrations of extended life spans through increased antioxidants have involved targeting those antioxidants to the mitochondria. "Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased expression of SIRT3 has been linked to an extended life span in humans. ... Of the 7 SIRT analogues, SIRT3 is the only member whose increased expression has been linked to the longevity of humans. Polymorphism in the SIRT3 gene promoter, which leads to gene activation, has been found to be associated with an extended life span of man. The molecular basis of SIRT3-dependent longevity is, however, not known. ... In primary cultures of cardiomyocytes, Sirt3 blocked cardiac hypertrophy by activating the forkhead box O3a–dependent (Foxo3a-dependent), antioxidant–encoding genes manganese superoxide dismutase (MnSOD) and catalase (Cat), thereby decreasing cellular levels of ROS. ... These results demonstrate that SIRT3 [protects] hearts by suppressing cellular levels of ROS."


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