DNA methylation-based estimator of telomere length

Ake T. Lu, Anne Seeboth, Pei Chien Tsai, Dianjianyi Sun, Austin Quach, Alex P. Reiner, Charles Kooperberg, Luigi Ferrucci, Lifang Hou, Andrea A. Baccarelli, Yun Li, Sarah E. Harris, Janie Corley, Adele Taylor, Ian J. Deary, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Wei Chen, Shengxu LiMassimo Mangino, Jordana T. Bell, James G. Wilson, Abraham Aviv, Riccardo E. Marioni, Kenneth Raj, Steve Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary 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.

Original languageEnglish (US)
Pages (from-to)5895-5923
Number of pages29
JournalAging
Volume11
Issue number16
DOIs
StatePublished - Jan 1 2019

Fingerprint

Telomere
DNA Methylation
Leukocytes
Physical Fitness
Women's Health
Menopause
Epigenomics
Vegetables
Methylation
Coronary Disease
Cultured Cells
Fishes
Heart Failure
Biomarkers
Smoking
History
Parturition
Pathology

Keywords

  • Aging
  • DNA methylation
  • Molecular biomarker
  • Telomere length

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Lu, A. T., Seeboth, A., Tsai, P. C., Sun, D., Quach, A., Reiner, A. P., ... Horvath, S. (2019). DNA methylation-based estimator of telomere length. Aging, 11(16), 5895-5923. https://doi.org/10.18632/aging.102173
Lu, Ake T. ; Seeboth, Anne ; Tsai, Pei Chien ; Sun, Dianjianyi ; Quach, Austin ; Reiner, Alex P. ; Kooperberg, Charles ; Ferrucci, Luigi ; Hou, Lifang ; Baccarelli, Andrea A. ; Li, Yun ; Harris, Sarah E. ; Corley, Janie ; Taylor, Adele ; Deary, Ian J. ; Stewart, James D. ; Whitsel, Eric A. ; Assimes, Themistocles L. ; Chen, Wei ; Li, Shengxu ; Mangino, Massimo ; Bell, Jordana T. ; Wilson, James G. ; Aviv, Abraham ; Marioni, Riccardo E. ; Raj, Kenneth ; Horvath, Steve. / DNA methylation-based estimator of telomere length. In: Aging. 2019 ; Vol. 11, No. 16. pp. 5895-5923.
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title = "DNA methylation-based estimator of telomere length",
abstract = "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 ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary 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.",
keywords = "Aging, DNA methylation, Molecular biomarker, Telomere length",
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Lu, AT, Seeboth, A, Tsai, PC, Sun, D, Quach, A, Reiner, AP, Kooperberg, C, Ferrucci, L, Hou, L, Baccarelli, AA, Li, Y, Harris, SE, Corley, J, Taylor, A, Deary, IJ, Stewart, JD, Whitsel, EA, Assimes, TL, Chen, W, Li, S, Mangino, M, Bell, JT, Wilson, JG, Aviv, A, Marioni, RE, Raj, K & Horvath, S 2019, 'DNA methylation-based estimator of telomere length', Aging, vol. 11, no. 16, pp. 5895-5923. https://doi.org/10.18632/aging.102173

DNA methylation-based estimator of telomere length. / Lu, Ake T.; Seeboth, Anne; Tsai, Pei Chien; Sun, Dianjianyi; Quach, Austin; Reiner, Alex P.; Kooperberg, Charles; Ferrucci, Luigi; Hou, Lifang; Baccarelli, Andrea A.; Li, Yun; Harris, Sarah E.; Corley, Janie; Taylor, Adele; Deary, Ian J.; Stewart, James D.; Whitsel, Eric A.; Assimes, Themistocles L.; Chen, Wei; Li, Shengxu; Mangino, Massimo; Bell, Jordana T.; Wilson, James G.; Aviv, Abraham; Marioni, Riccardo E.; Raj, Kenneth; Horvath, Steve.

In: Aging, Vol. 11, No. 16, 01.01.2019, p. 5895-5923.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA methylation-based estimator of telomere length

AU - Lu, Ake T.

AU - Seeboth, Anne

AU - Tsai, Pei Chien

AU - Sun, Dianjianyi

AU - Quach, Austin

AU - Reiner, Alex P.

AU - Kooperberg, Charles

AU - Ferrucci, Luigi

AU - Hou, Lifang

AU - Baccarelli, Andrea A.

AU - Li, Yun

AU - Harris, Sarah E.

AU - Corley, Janie

AU - Taylor, Adele

AU - Deary, Ian J.

AU - Stewart, James D.

AU - Whitsel, Eric A.

AU - Assimes, Themistocles L.

AU - Chen, Wei

AU - Li, Shengxu

AU - Mangino, Massimo

AU - Bell, Jordana T.

AU - Wilson, James G.

AU - Aviv, Abraham

AU - Marioni, Riccardo E.

AU - Raj, Kenneth

AU - Horvath, Steve

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary 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.

AB - 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 ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary 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.

KW - Aging

KW - DNA methylation

KW - Molecular biomarker

KW - Telomere length

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Lu AT, Seeboth A, Tsai PC, Sun D, Quach A, Reiner AP et al. DNA methylation-based estimator of telomere length. Aging. 2019 Jan 1;11(16):5895-5923. https://doi.org/10.18632/aging.102173