Genome survey for loci that influence successful aging: results at 10-cM resolution.
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.
Zubenko
George S
GS
Department of Psychiatry, University of Pittsburgh, School of Medicine, PA, USA. zubenkog@pitt.edu
Hughes
Hugh B
HB
Zubenko
Wendy N
WN
Maher
Brion S
BS
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003071:Cognition / Q000502:physiology*; D004247:DNA / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D009483:Neuropsychological Tests; D010414:Pennsylvania; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D012737:Sex Factors; D012959:Socioeconomic Factors; D020080:Tandem Repeat Sequences / Q000235:genetics; D044465:White People / Q000235:genetics
D004247:DNA