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Genome Survey for Loci That Influence Successful Aging: Results at 10-cM Resolution

From the Department of Psychiatry, University of Pittsburgh, School of Medicine (GSZ, HBH, WNZ); the Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University (GSZ); and the Center for Craniofacial and Dental Genetics, University of Pittsburgh, School of Dental Medicine (BSM), Pittsburgh, PA.

Objective: A systematic genome survey was initiated to identify loci that affect the likelihood of reaching age 90 with preserved cognition (successful aging).

Methods: The genome survey was conducted at 10-cM resolution for simple sequence tandem repeat polymorphisms (SSTRPs) that identify genes for Successful AGing (SAG loci) by virtue of linkage disequilibrium. Efficiency was enhanced by genotyping pools of DNA from 100 cognitively intact elders and 100 young (18–25 years) adults. The comparison groups included equal numbers of white men and women of similar ethnicity that were recruited from the southwestern Pennsylvania region.

Results: Our genome survey identified nine SAG candidate loci that may influence the likelihood of reaching age 90 or more with preserved cognition. Two of the autosomal SAG loci revealed stronger allelic associations with successful aging in men than women (D1S1728, D8S264) and two were located on sex chromosomes (DXS9902, DYS390). DXS9902 resides within a predicted gene, whereas six of the SAG loci are located within regions previously reported to show linkage to other phenotypes.

Conclusions: The results of our study suggest that loci with differential effects on the successful aging of men and women may be common. The majority of the SAG candidate loci detected in this study overlap with regions previously reported to show linkage to susceptibility genes for cardiovascular disorders, psychiatric disorders, and the accumulation of tissue damage resulting from oxidative stress.

Key Words: Genetics • genome survey • successful aging • nonagenarians • longevity • preserved cognition • sex effects

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