Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly.
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.
Department of Cell Biology, University of Calabria, Rende 87030, Italy.
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Rose
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Altomare
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Bellizzi
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Garasto
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Greco
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Passarino
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Feraco
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Mari
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Franceschi
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De Benedictis
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D056566:Sirtuin 3; D037761:Sirtuins / Q000235:genetics*; D015996:Survival Rate
D024101:Mitochondrial Proteins; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D037761:Sirtuins; D006655:Histone Deacetylases