A genome-wide scan for linkage to human exceptional longevity identifies alocus on chromosome 4

Substantial evidence supports the familial aggregation of exceptional longe vity. The existence of rare families demonstrating clustering for this phen otype suggests that a genetic etiology may be an important component. Previ ous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In th is study, a genome-wide scan for such predisposing loci was conducted by us ing 308 individuals belonging to 137 sibships demonstrating exceptional lon gevity. By using nonparametric analysis, significant evidence for linkage w as noted for chromosome 4 at D4S1564 with a MLS of 3.65 (P = 0.044). The an alysis was corroborated by a parametric analysis (P = 0.052). These linkage results indicate the likelihood that there exists a gene, or genes, that e xerts a substantial influence on the ability to achieve exceptional old age . Identification of the genes in humans that allow certain individuals to l ive to extreme old age should lead to insights on cellular pathways that ar e important to the aging process.