Journal
AGING-US
Volume 11, Issue 16, Pages 5895-5923Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102173
Keywords
telomere length; DNA methylation; molecular biomarker; aging
Categories
Funding
- NIH/NIEHS [R01-ES020836]
- National Institute of General Medical Sciences [U54GM115428]
- National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]
- National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]
- National Institute on Minority Health and Health Disparities [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]
- National Institutes of Health [N01-HC-25195, HHSN268201500001I]
- Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
- Division of Intramural Research, National Heart, Lung, and Blood Institute
- Center for Information Technology, National Institutes of Health, Bethesda, MD
- National Institute for Health Research through the Health Protection Research Unit, Health Impact of Environmental Hazards
- UK's Biotechnology and Biological Sciences Research Council (BBSRC)
- Royal Society-Wolfson Research Merit Award
- Chief Scientist Office (CSO) of the Scottish Government's Health Directorates
- UK (Disconnected Mind program)
- Medical Research Council [MR/M01311/1]
- Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award)
- Age UK
- Wellcome Trust Institutional Strategic Support Fund
- University of Edinburgh
- University of Queensland
- Alzheimer's Research UK [ARUK-PG2017B-10]
- Medical Research Council PhD Studentship in Precision Medicine
- Medical Research Council Doctoral Training Programme
- University of Edinburgh College of Medicine and Veterinary Medicine
- Wellcome Trust
- European Community's Seventh Framework Programme (FP7/2007-2013)
- National Institute for Health Research (NIHR)
- ESRC UK [ES/N000404/1]
- [1U01AG060908 - 01]
- BBSRC [BB/F019394/1] Funding Source: UKRI
- ESRC [ES/N000404/1] Funding Source: UKRI
Ask authors/readers for more resources
Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r (similar to)-0.75 for DNAmTL versus r (similar to) -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-tocoronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.
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