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J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1448-1452. doi: 10.1093/gerona/gly071.

Minimal Shortening of Leukocyte Telomere Length Across Age Groups in a Cross-Sectional Study for Carriers of a Longevity-Associated FOXO3 Allele.

Author information

1
Institute for Biogenesis Research, University of Hawaii, Honolulu.
2
Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu.
3
Department of Human Welfare, Okinawa International University, Ginowan, Japan.
4
Okinawa Research Center for Longevity Science, Japan.
5
Department of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Japan.
6
Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
7
Diabetes and Life-Style Related Disease Center, Tomishiro Central Hospital, Okinawa, Japan.
8
Ohana Genetics, Honolulu, Hawaii.
9
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
10
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
11
Spinal Cord Injury and Disorders Program, VA Pacific Islands Health Care System, Honolulu, Hawaii.
12
School of Medical Sciences and Bosch Institute, University of Sydney, New South Wales, Australia.
13
Office of Biostatistics and Quantitative Sciences, John A. Burns School of Medicine, University of Hawaii, Honolulu.
14
Pacific Health Research and Education Institute, Honolulu, Hawaii.

Abstract

FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprised of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50 years of age) participants. This is the first validated longevity gene variant identified to date showing an association with negligible loss of telomere length with age in humans in a cross-sectional study. Reduced telomere attrition may be a key mechanism for the longevity-promoting effect of the FOXO3 genotype studied.

PMID:
29688278
PMCID:
PMC6175018
[Available on 2019-10-08]
DOI:
10.1093/gerona/gly071
[Indexed for MEDLINE]
Free PMC Article

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