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Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland
Department of Neurology, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland
Department of Ophthalmology, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland
* Author to whom correspondence should be addressed.
Received: 2 January 2013; in revised form: 25 January 2013 / Accepted: 29 January 2013 / Published: 11 February 2013
Abstract: Increased oxidative stress has been associated with the aging process. However, recent studies have revealed that a low-level oxidative stress can even extend the lifespan of organisms. Reactive oxygen species (ROS) are important signaling molecules, e.g., being required for autophagic degradation. SIRT1, a class III protein deacetylase, is a crucial cellular survival protein, which is also involved in combatting oxidative stress. For instance, SIRT1 can stimulate the expression of antioxidants via the FoxO pathways. Moreover, in contrast to ROS, SIRT1 inhibits NF-κB signaling which is a major inducer of inflammatory responses, e.g., with inflammasome pathway. Recent studies have demonstrated that an increased level of ROS can both directly and indirectly control the activity of SIRT1 enzyme. For instance, ROS can inhibit SIRT1 activity by evoking oxidative modifications on its cysteine residues. Decreased activity of SIRT1 enhances the NF-κB signaling, which supports inflammatory responses. This crosstalk between the SIRT1 and ROS signaling provokes in a context-dependent manner a decline in autophagy and a low-grade inflammatory phenotype, both being common hallmarks of ageing. We will review the major mechanisms controlling the signaling balance between the ROS production and SIRT1 activity emphasizing that this crosstalk has a crucial role in the regulation of the aging process.
Keywords: ageing; autophagy; oxidative stress; inflammasome; NF-κB; ROS; SIRT1
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Salminen, A.; Kaarniranta, K.; Kauppinen, A. Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process. Int. J. Mol. Sci. 2013, 14, 3834-3859.
Salminen A, Kaarniranta K, Kauppinen A. Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process. International Journal of Molecular Sciences. 2013; 14(2):3834-3859.
Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu. 2013. "Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process." Int. J. Mol. Sci. 14, no. 2: 3834-3859.