Cited by 367Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsGenomics and Chromatin Dynamics

A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages

Bellizzi, Dina, Rose, Giuseppina, Cavalcante, Paola, Covello, Giuseppina, Dato, Serena, De Rango, Francesco, Greco, Valentina, Maggiolini, Marcello +5 more·2005·Genomics

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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Crossref · 10.1016/j.ygeno.2004.11.003

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  • The tumor suppressing contributions of SirT3 could partially explain why a polymorphism in intron 5 of human SirT3 associated with higher SirT3 expression is associated with increased longevity.

    “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).”

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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)
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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