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Oncotarget. 2015 Feb 28;6(6):3600-12.

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

Author information

1
Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
2
Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
3
Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
4
Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, 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.

PMID:
25682868
PMCID:
PMC4414140
DOI:
10.18632/oncotarget.2877
[Indexed for MEDLINE]
Free PMC Article

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