Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival

Sangkyu Kim, Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
David A. Welsh, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Leann Myers, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Katie E. Cherry, Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, USA.
Jennifer Wyckoff, Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
S Michal Jazwinski, Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.

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.

This paper has been withdrawn.