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 language | English (US) |
|---|---|
| Pages (from-to) | 5895-5923 |
| Number of pages | 29 |
| Journal | Aging |
| Volume | 11 |
| Issue number | 16 |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Aging
- DNA methylation
- Molecular biomarker
- Telomere length
ASJC Scopus subject areas
- Aging
- Cell Biology
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85071788563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071788563&partnerID=8YFLogxK
U2 - 10.18632/aging.102173
DO - 10.18632/aging.102173
M3 - Article
C2 - 31422385
AN - SCOPUS:85071788563
VL - 11
SP - 5895
EP - 5923
JO - Aging
JF - Aging
SN - 1945-4589
IS - 16
ER -