Journal
TRENDS IN MOLECULAR MEDICINE
Volume 23, Issue 4, Pages 320-331Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2017.02.005
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Funding
- NIH [DK103295]
- Glenn Foundation for Medical Research
- Portuguese Foundation for Science and Technology (FCT-MCTES)
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Advancing age is the major risk factor for the development of chronic diseases and is accompanied by changes in metabolic processes and mitochondrial dysfunction. Mitochondrial sirtuins (SIRT3-5) are part of the sirtuin family of NAD(+)-dependent deacylases and ADP-ribosyl transferases. The dependence on NAD(+) links sirtuin enzymatic activity to the metabolic state of the cell, poising them as stress sensors. Recent insights have revealed that SIRT3-5 orchestrate stress responses through coordinated regulation of substrate clusters rather than of a few key metabolic enzymes. Additionally, mitochondrial sirtuin function has been implicated in the protection against age-related pathologies, including neurodegeneration, cardiopathologies, and insulin resistance. In this review, we highlight the molecular targets of SIRT3-5 and discuss their involvement in aging and age-related pathologies.
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