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Cell. 2016 May 5;165(4):1002-11. doi: 10.1016/j.cell.2016.03.022. Epub 2016 Apr 21.

Whole-Genome Sequencing of a Healthy Aging Cohort.

Author information

1
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA 22042 USA.
3
Cypher Genomics, Inc., San Diego, CA 92121, USA.
4
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA 22042 USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
5
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: etopol@scripps.edu.
6
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA; Cypher Genomics, Inc., San Diego, CA 92121, USA. Electronic address: atorkama@scripps.edu.

Abstract

Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors. VIDEO ABSTRACT.

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PMID:
27114037
PMCID:
PMC4860090
DOI:
10.1016/j.cell.2016.03.022
[Indexed for MEDLINE]
Free PMC Article

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