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 possib...

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Bibliographic Details
Published in:Experimental gerontology 2003-10, Vol.38 (10), p.1065-1070
Main Authors: Rose, G, Dato, S, Altomare, K, Bellizzi, D, Garasto, S, Greco, V, Passarino, G, Feraco, E, Mari, V, Barbi, C, BonaFe, M, Franceschi, C, Tan, Q, Boiko, S, Yashin, A.I, De Benedictis, G
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Chromosomes, Human, Pair 11 - genetics
Female
Genotype
Haplotypes
Histone Deacetylases - genetics
Human longevity
Humans
Linkage Disequilibrium
Longevity - genetics
Male
Middle Aged
Mitochondrial Proteins - genetics
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Silent Information Regulator 2 homologue
SIRT3 gene
Sirtuin 3
Sirtuins - genetics
Survival Rate
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Summary: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.
ISSN:0531-5565
1873-6815
DOI:10.1016/S0531-5565(03)00209-2