The DOI matches its Crossref record; 26 of the 27 references it cites were found in a registry or an index.
A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages
Abstract
SIR2 genes control life span in model organisms, playing a central role in evolutionarily conserved pathways of aging and longevity. We wanted to verify whether similar effects may act in humans too. First, we searched for variability in the human sirtuin 3 gene (SIRT3) and discovered a VNTR polymorphism (72-bp repeat core) in intron 5. The alleles differed both for the number of repeats and for presence/absence of potential regulatory sites. Second, by transient transfection experiments, we demonstrated that the VNTR region has an allele-specific enhancer activity. Third, by analyzing allele frequencies as a function of age in a sample of 945 individuals (20-106 years), we found that the allele completely lacking enhancer activity is virtually absent in males older than 90 years. Thus the underexpression of a human sirtuin gene seems to be detrimental for longevity as it occurs in model organisms.
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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 Bellizzi et al., 2005
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Cites
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1 of the 27 references couldn’t be matched to a known paper.
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Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014) · Physiological Reviews · doi:10.1152/physrev.00026.2013 · Cited by 5,383
Mammalian Sirtuins: Biological Insights and Disease Relevance
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Sirtuins in mammals: insights into their biological function
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Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
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Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
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Metadata
- Authors
- Bellizzi, D., Rose, G., Cavalcante, P., Covello, G., Dato, S., De Rango, F., Greco, V., Maggiolini, M., Feraco, E., Mari, V., Franceschi, C., Passarino, G., & De Benedictis, G.
- Affiliations
- University of Calabria (IT)
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- ORCID
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 85
- Issue
- 2
- Pages
- 258-263
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2095106276
- Cited by
- 367
- References
- 27
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 9 · 2021: 21 · 2020: 16 · 2019: 15 · 2018: 17 · 2017: 20 · 2016: 26 · 2015: 26 · 2014: 21 · 2013: 29 · 2012: 17
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (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 › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SIRT3, VNTR polymorphism, intron 5, enhancer activity, allele-specific expression, longevity, oldest old, aging, gene expression regulation, repeat number variation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Base Sequence, Enhancer Elements, Genetic, Female, Histone Deacetylases, Humans, Longevity, Male, Middle Aged, Molecular Sequence Data, Polymorphism, Genetic, Minisatellite Repeats, Mitochondrial Proteins, Sirtuins, Sirtuin 3
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