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

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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, Feraco, Emidio, Mari, Vincenzo, Franceschi, Claudio, Passarino, Giuseppe, De Benedictis, Giovanna·2005·Genomics

DOI 10.1016/j.ygeno.2004.11.003

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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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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: Bellizzi, Dina
Rose, Giuseppina
Cavalcante, Paola
Covello, Giuseppina
Dato, Serena
Maggiolini, Marcello
Franceschi, Claudio
Passarino, Giuseppe
Venue: Genomics
Publisher: Elsevier BV
Published: 2005-02
Volume: 85
Issue: 2
Pages: 258-263
ISSN: 0888-7543 (ISSN-L)
DOI: 10.1016/j.ygeno.2004.11.003
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages

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