Molecular Switch May Underlie Diseases of Aging
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Posted on Dec 30, 2014, 6 a.m.
Scientists have identified a single molecular switch controlling inflammatory processes that may underlie aging-related diseases.
Studies have implicated a role for nitric oxide in diabetes, neurodegeneration, atherosclerosis and other aging-related disorders known to involve chronic inflammation. But exactly how nitric oxide exerts those effects - including activation of the inflammatory factor NF-kappaB and the regulatory protein p53, which can induce the death of damaged cells – has remained unknown. SIRT1 is known to suppress the activity of both NF-kappaB and p53, and since its dysregulation has been associated with models of several aging-related conditions, the research team focused on nitric oxide's suppression of SIRT1 through a process called S-nitrosylation. Cellular experiments revealed that S-nitrosylation inactivates SIRT1 by interfering with the protein's ability to bind zinc, which in turn increases the activation of p53 and of a protein subunit of NF-kappaB. The study authors submit that: “S-nitrosylation of SIRT1 may represent a proinflammatory switch common to many diseases and aging.”
Shinozaki S, Chang K, Sakai M, Shimizu N, Yamada M, Kaneki M, et al. “Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65.” Sci Signal. 2014 Nov 11;7(351):ra106.