Role of sirtuin genes in longevity

An organism’s ability to regulate gene expression in response to environmental factors such as nutrition levels and oxygen availability is critical for survival. Previous research has implicated sirtuin genes, which transcribe deacetylase proteins that regulate gene expression via deacetylase of either histone proteins or other proteins, in regulation of both oxygen and nutrient availability in mice. This research knocks down sirtuins in the dietary restriction pathway and the hypoxic response pathways in order to examine whether these molecular pathways act in a sirtuin-dependent mechanism in Caenorhabditis elegans. The findings showed that in both pathways, knockdown of sirtuin-dependent gene expression led to a decreased lifespan but did not mirror the lifespan of the worm strains that were either sirtuin mutant strains or sirtuin RNAi knockdowns in wild type worm strains. This indicates that both pathways are not sirtuin-dependent, although the mechanism of how these pathways increase longevity remains unclear. These findings point to the need for further research into the role of sirtuin genes within the cell and whether they actually function as longevity genes.