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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.
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“The tumor suppressing contributions of SirT3 could partially explain why a polymorphism in a variable number tandem repeat regions within intron 5 of the human SirT3 gene, which results in higher than normal expression of SirT3, is associated with increased longevity in humans (Rose et al., 2003; Bellizzi et al., 2005).”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Rose et al., 2003
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Metadata
- 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.
- Affiliations
- University of Calabria (IT)
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- University of Southern Denmark (DK)
- Max Planck Institute for Demographic Research (DE)
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 38
- Issue
- 10
- Pages
- 1065-1070
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2077864684
- Cited by
- 282
- References
- 27
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 17 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 16 · 2015: 18 · 2014: 15 · 2013: 29 · 2012: 16
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- SIRT3, sirtuins, genetic variation, human longevity, linkage disequilibrium, 11p15.5, HRAS1, insulin-like growth factor II, proinsulin, tyrosine hydroxylase, mitochondrial deacetylase, lifespan
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11, Female, Genotype, Haplotypes, Histone Deacetylases, Humans, Longevity, Male, Middle Aged, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length, Linkage Disequilibrium, Survival Rate, Mitochondrial Proteins, Sirtuins, Sirtuin 3
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