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

Exp Gerontol. 2003 Oct;38(10):1065-70. doi: 10.1016/s0531-5565(03)00209-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, Pair 11 / genetics
  • Female
  • Genotype
  • Haplotypes
  • Histone Deacetylases / genetics*
  • Humans
  • Linkage Disequilibrium
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Sirtuin 3
  • Sirtuins / genetics*
  • Survival Rate


  • Mitochondrial Proteins
  • SIRT3 protein, human
  • Sirtuin 3
  • Sirtuins
  • Histone Deacetylases