title: Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival.
abstract: We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13-14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity.
authors: Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Sangkyu
authors: S
authors: Kim
authors: Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors: David A
authors: DA
authors: Welsh
authors: Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Leann
authors: L
authors: Myers
authors: Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, USA.
authors: Katie E
authors: KE
authors: Cherry
authors: Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Jennifer
authors: J
authors: Wyckoff
authors: Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: S Michal
authors: SM
authors: Jazwinski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide