Lifespan Extension by Red Wine Ingredient Resveratrol Linked to Methylation Following Action on SirT1

in medicine, biology

A new research suggests that the protein target of the red wine ingredient resveratrol may be extending lifespan by a new mechanism.  The protein target of resveratrol in mammals is the enzyme called SirT1, which belongs to a family of proteins called sirtuins.
 
The function of SirT1 is to catalyze the removal of a chemical group called acetyl group from other proteins. The  deacetylation changes the activity of these proteins, most of them serving critical functions. This critical function of SirT1 was believed to be important in extending life span in some animals such as worms, flies and mice. 
 
During the catalytic process, SirT1 also converts a molecule called nicotinamide adenine dinucleotide (NAD) into nicotinamide (NAM).  The new research report suggests that the end product NAM is further methylated by another enzyme called methyltransferase, encoded by a gene called anmt-1 to generate MNA, or methyl nicotinamide. The scientists say that the methyl nicotinamide produced by this reaction generates a signal that extends life.  This signal is hydrogen peroxide, a reactive oxygen species (ROS). Excess hydrogen peroxide or ROS generation has always been considered to be detrimental to the cells.
 
The research report by the multinational group of researchers led by Dr. David Sinclair of Harvard and Michael Ristow of University of Jena, Germany, was published recently in the reputed journal Nature Chemical Biology.
 
According to the paper, the scientists identified a previously unnown methyltransferase that produce MNA from NAM by specific methylation. MNA is substrate for another enzyme that acts on it to generate hydrogen peroxide, a reactive oxygen species.
 
The authors concluded that sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.

Science Story Reference: 

Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, Heiland I, Birringer M, Groth M, Segref A, Kanfi Y, Price NL, Schmeisser S, Schuster S, Pfeiffer AF, Guthke R, Platzer M, Hoppe T, Cohen HY, Zarse K, Sinclair DA, Ristow M. Nat Chem Biol. 2013 Sep 29. doi: 10.1038/nchembio.1352.

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