An allele of HRAS1 3'variable number of tandem repeats is a frailty allele: implication for an evolutionarily-conserved pathway involved in longevity.
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.
Bonafè
Massimiliano
M
Department of Experimental Pathology, University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy.
Barbi
Cristiana
C
Olivieri
Fabiola
F
Yashin
Anatoli
A
Andreev
Kirill F
KF
Vaupel
James W
JW
De Benedictis
Giovanna
G
Rose
Giuseppina
G
Carrieri
Giuseppina
G
Jazwinski
S Michal
SM
Franceschi
Claudio
C
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*
D004272:DNA, Mitochondrial