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Received December 17, 2001; revised February 4, March 4, 2002; accepted March 12, 2002. From the Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA (GSZ,SS,HBH,MJF,WNZ), and the Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, PA (GSZ). Address correspondence to Dr. George S. Zubenko, WPIC, Room E1230, 3811 O'Hara Street, Pittsburgh, PA 15213. e-mail: zubenkog{at}pitt.edu
OBJECTIVE: A systematic genome survey was initiated to identify loci that affect the likelihood of reaching age 90 with preserved cognition. This communication describes the clinical characterization and comparison of the experimental groups, validation of the experimental method, and results for the Y chromosome. METHODS: The genome survey was conducted at 10 cM resolution for simple sequence tandem repeat polymorphisms (SSTRPs) that identify genes for successful aging by virtue of linkage disequilibrium. Efficiency was enhanced by genotyping pools of DNA from 100 cognitively intact elders (50 men/50 women) and 100 young (age 18–25 years) adults matched for sex, race, ethnicity, and geographic location. RESULTS: Elders (94 nonagenarians, 6 centenarians) manifested preserved cognition, as reflected by clinical and psychometric assessments; "good" average capacity to carry out their activities of daily living; and the majority were living independently despite multiple medical conditions. None had a history of mental disorders in early or middle adulthood, only one was a current smoker, and 80% consumed alcohol less than once each month. The genome survey method detected the expected elevation of the APOE 
2 allele frequency, and reciprocal reduction in the 4 frequency, among the elders, compared with the young adults. It also detected significant differences in the allelic distributions of DYS389 and DYS390, which are separated by only 2.6 Mb near the centromere of Yq. CONCLUSIONS: These results suggest that several behavioral and genetic factors may contribute to the likelihood of achieving exceptional longevity with preserved cognition.
Key Words: Successful Aging • Genetic Factors
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