DhHP-6 Extends Caenorhabditis elegans Lifespan in a SIR2.1Dependent Manner

摘要

SIR2 (silent mating type information regulation-2) and its orthologs represent a conserved group of genes encoding NAD~+-dependent protein deacetylases that play important roles in lifespanextending effects [1], Increased dosage of SIR2 orthologs from S. cerevlsiae, D. melanogaster, and C. elegans extend their lifespan, suggesting that Sir2 genes are conserved "regulators of the aging process [2]. In C. elegans, it has been identified that SIR-2.1 functions through 14-3-3 proteins and affect DAF-16 transcriptional activity [3]. DhHP-6 is a nonapeptide that contains deuterohaemin and histidine. It was designed as a mimetic of peroxidase. Our recent studies show that DhHP-6 extends the lifespan of wild type C. elegans by 20%. Here we found that DhHP-6 treatment up-regulates sir-2.1 gene encoding SIR2 like protein in C. elegans and the lifespan extension by DhHP-6 is also dependent upon sir-2.1. We predict that DhHP-6's lifespan extension effect is mediated by sir-2.1/DAF-16 pathway.