title: An allele of HRAS1 3'variable number of tandem repeats is a frailty allele: implication for an evolutionarily-conserved pathway involved in longevity.
abstract: The human HRAS1 belongs to an evolutionarily-conserved family of genes which enrolls among its members the yeast RAS2, a gene which regulates stress response and longevity in the Saccharomyces cerevisiae. In this paper we report that the frequency of the a3 allele of HRAS1 3'variable number tandem repeat (HRAS1 3'VNTR) decreases in centenarians in respect to young people, and we estimate that during aging a3 carriers have a relative mortality risk of 1.126 (95% CI=1.044-1.213). We propose that the germ-line variability at the HRAS1 locus impacts on the individual's capacity to reach the extreme limits of human life-span. Furthermore, we provide suggestive evidence that a3 HRAS1 3'VNTR allele and inherited variants of the mitochondrial genome (mtDNA haplogroups) do not affect independently human longevity, thus recalling the nucleus-mitochondrion interaction which regulates stress response and life-span in the yeast.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafè
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbi
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.forename: Anatoli
authors.initials: A
authors.lastname: Yashin
authors.forename: Kirill F
authors.initials: KF
authors.lastname: Andreev
authors.forename: James W
authors.initials: JW
authors.lastname: Vaupel
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Benedictis
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rose
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Carrieri
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004272:DNA, Mitochondrial / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008136:Longevity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial