Pii: S0378-1119(01)00812-5

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 0variable number tandem repeat (HRAS1 3 0VNTR) 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 1⁄4 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 0VNTR 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. q 2002 Elsevier Science B.V. All rights reserved.