A byproduct of sirtuin enzyme reaction, which had been thought to be unimportant, plays a direct role in Caenorhabditis elegans worm aging, according to a paper published online this week in Nature Chemical Biology. These result suggest that an important aspect of sirtuin activity may have been overlooked and point to new mechanisms for possibly extending lifespan.
Sirtuin enzymes are involved in modifying histones, protein complexes that allow tight packing and storage of DNA. In many organisms, sirtuins have also been linked to regulating DNA health and therefore longevity, but it is unclear how these enzymes, and the modifications they make, are linked to longevity.
Michael Ristow and colleagues show that the conversion of nicotinamide adenine dinucleotide (NAD+) to nicotinamide during the course of the sirtuin reaction has an unexpectedly strong impact on increasing lifespan in C. elegans. The authors report that sirtuins are expendable if nicotinamide or a subsequent product, 1-methylnicotinamide, are directly added to cells or C. elegans.