Molecular Switch May Underlie Diseases of Aging

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.”