TY - JOUR
T1 - An allele of HRAS1 3′variable number of tandem repeats is a frailty allele
T2 - Implication for an evolutionarily-conserved pathway involved in longevity
AU - Bonafè, Massimiliano
AU - Barbi, Cristiana
AU - Olivieri, Fabiola
AU - Yashin, Anatoli
AU - Andreev, Kirill F.
AU - Vaupel, James W.
AU - De Benedictis, Giovanna
AU - Rose, Giuseppina
AU - Carrieri, Giuseppina
AU - Jazwinski, S. Michal
AU - Franceschi, Claudio
PY - 2002/3/6
Y1 - 2002/3/6
N2 - 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.
AB - 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.
KW - Aging
KW - HRAS1 polymorphisms
KW - Ras genes
KW - Retrograde response
KW - Stress response
UR - http://www.scopus.com/inward/record.url?scp=0037029127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037029127&partnerID=8YFLogxK
U2 - 10.1016/S0378-1119(01)00812-5
DO - 10.1016/S0378-1119(01)00812-5
M3 - Article
C2 - 11943467
AN - SCOPUS:0037029127
VL - 286
SP - 121
EP - 126
JO - Gene
JF - Gene
SN - 0378-1119
IS - 1
ER -