DNA methylation GrimAge strongly predicts lifespan and healthspan

Ake T. Lu, Austin Quach, James G. Wilson, Alex P. Reiner, Abraham Aviv, Kenneth Raj, Lifang Hou, Andrea A. Baccarelli, Yun Li, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Luigi Ferrucci, Steve Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based estimators of plasma proteins including those of plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. The resulting predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogates and a DNAm-based estimator of smoking packyears. Adjusting DNAm GrimAge for chronological age generated novel measure of epigenetic age acceleration, AgeAccelGrim. Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E- 75), time-to-coronary heart disease (P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E- 17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P= 7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment. Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies.

Original languageEnglish (US)
Pages (from-to)303-327
Number of pages25
JournalAging
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2019

Fingerprint

DNA Methylation
Epigenomics
Biomarkers
Plasminogen Activator Inhibitor 1
Comorbidity
Blood Proteins
Growth Differentiation Factor 15
Aptitude
Intra-Abdominal Fat
Fatty Liver
Menopause
Type 2 Diabetes Mellitus
Coronary Disease
Life Style
Smoking
Tomography

Keywords

  • DNA methylation
  • Epigenetics
  • Mortality
  • Proteomics

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Lu, A. T., Quach, A., Wilson, J. G., Reiner, A. P., Aviv, A., Raj, K., ... Horvath, S. (2019). DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging, 11(2), 303-327. https://doi.org/10.18632/aging.101684
Lu, Ake T. ; Quach, Austin ; Wilson, James G. ; Reiner, Alex P. ; Aviv, Abraham ; Raj, Kenneth ; Hou, Lifang ; Baccarelli, Andrea A. ; Li, Yun ; Stewart, James D. ; Whitsel, Eric A. ; Assimes, Themistocles L. ; Ferrucci, Luigi ; Horvath, Steve. / DNA methylation GrimAge strongly predicts lifespan and healthspan. In: Aging. 2019 ; Vol. 11, No. 2. pp. 303-327.
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Lu, AT, Quach, A, Wilson, JG, Reiner, AP, Aviv, A, Raj, K, Hou, L, Baccarelli, AA, Li, Y, Stewart, JD, Whitsel, EA, Assimes, TL, Ferrucci, L & Horvath, S 2019, 'DNA methylation GrimAge strongly predicts lifespan and healthspan', Aging, vol. 11, no. 2, pp. 303-327. https://doi.org/10.18632/aging.101684

DNA methylation GrimAge strongly predicts lifespan and healthspan. / Lu, Ake T.; Quach, Austin; Wilson, James G.; Reiner, Alex P.; Aviv, Abraham; Raj, Kenneth; Hou, Lifang; Baccarelli, Andrea A.; Li, Yun; Stewart, James D.; Whitsel, Eric A.; Assimes, Themistocles L.; Ferrucci, Luigi; Horvath, Steve.

In: Aging, Vol. 11, No. 2, 01.01.2019, p. 303-327.

Research output: Contribution to journalArticle

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Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging. 2019 Jan 1;11(2):303-327. https://doi.org/10.18632/aging.101684