Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly

Abstract

The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin 2 proteins. Studies in model organisms have demonstrated that SIR2 genes control lifespan, while no data are available regarding a possible role of SIRT3 in human longevity. By analysing the genotype-specific survival function relevant to the G477T marker of SIRT3, we found that in males the TT genotype increases (p=0.0272), while the GT genotype decreases (p=0.0391) survival in the elderly. Since SIRT3 lies in a chromosomal region (11p15.5) where four genes potentially associated with longevity are located (HRAS1, Insulin-like Growth Factor 2, Proinsulin, and Tyrosine Hydroxylase) we tested for linkage-disequilibrium between G477T alleles and alleles of the above genes. The disequilibrium was not significant in any case, thus suggesting that SIRT3 itself, or a gene strictly linked to SIRT3, may have a role in human longevity.