The Relationship between the Sirtuins and Slowing the Aging

Sohair M. Khojah

Abstract

Originally rising to notoriety for their function in ‎regulating the aging, sirtuins are a group of NAD-dependent ‎enzymes that are related to a steadily increasing some biological ‎processes. In addition to controlling aging, sirtuins play key roles ‎in maintaining the organism metabolic homeostasis. These ‎enzymes have primarily preventative roles in the development of ‎many age-related diseases, including cancer, neurodegeneration, ‎and cardiovascular diseases. Seven isoforms of this enzyme have ‎been specified in mammals, (SIRT1–7), all of them involve a ‎conserved catalytic core and show differential subcellular ‎localization and activities. Oxidative stress can affect the activity ‎of sirtuins at different levels:  expression, post-translational ‎modifications, protein-protein interactions, and NAD levels. Mild ‎oxidative stress induces the expression of sirtuins as a ‎compensatory mechanism, while harsh or prolonged oxidant ‎conditions result in dysfunctional modified sirtuins more prone to ‎degradation by the proteases. Oxidative post-translational ‎modifications have been identified in vitro and in vivo, in ‎particular, cysteine oxidation and tyrosine nitration.‎ Nevertheless, further studies are necessary to find out the ‎molecular mechanisms of redox regulation of sirtuins to further ‎design appropriate pharmacological interventions‎‎‎.



Download PDF