title: Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study "Treviso Longeva (TRELONG)".
abstract: Human sirtuins are seven proteins with deacetylase activity that are emerging as key modulators of basic physiological functions. Some evidence links SIRT3 to longevity in mammals. This study aimed to investigate whether variants within SIRT3 gene were associated to human longevity. We analyzed 549 genomic DNA collected during the prospective study "Treviso Longeva," including elderly over 70 years of age from the municipality of Treviso, a small city in the northeast of Italy. We genotyped SIRT3 rs3825075, rs4980329, and rs11555236 single nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association among the SIRT3 SNPs and longevity. However, when we performed a longitudinal analysis considering mortality as a dependent variable, we observed an association of SIRT3 rs11555236 and rs4980329 with longevity in the whole population (p values corrected for potential confounders = 0.04 and 0.03, respectively). After stratification according to gender, the same SNPs were associated to female longevity only (p values corrected for potential confounders = 0.03 and 0.02, respectively). Finally, as rs11555236 was reported to be in linkage disequilibrium with a putative functional enhancer within the SIRT3 gene, we assessed whether rs11555236 genotypes correlated with a different level of SIRT3 protein in peripheral blood mononuclear cells. We found an increased level of SIRT3 in subjects homozygous for the (T) allele. We suggest that SIRT3 genetic variability might be relevant for the modulation of human longevity in the Italian population.
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156, Milan, Italy, diego.albani@marionegri.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ateri
authors.forename: Stefano
authors.initials: S
authors.lastname: Mazzuco
authors.forename: Alice
authors.initials: A
authors.lastname: Ghilardi
authors.forename: Serena
authors.initials: S
authors.lastname: Rodilossi
authors.forename: Gloria
authors.initials: G
authors.lastname: Biella
authors.forename: Fausta
authors.initials: F
authors.lastname: Ongaro
authors.forename: Piero
authors.initials: P
authors.lastname: Antuono
authors.forename: Paolo
authors.initials: P
authors.lastname: Boldrini
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Giorgi
authors.forename: Andrea
authors.initials: A
authors.lastname: Frigato
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Durante
authors.forename: Livio
authors.initials: L
authors.lastname: Caberlotto
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanardo
authors.forename: Marinella
authors.initials: M
authors.lastname: Siculi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gallucci
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015153:Blotting, Western; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D056566:Sirtuin 3 / Q000235:genetics*
chemical_list: C466093:SIRT3 protein, human; D056566:Sirtuin 3