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Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden

Hillary, Robert F., Stevenson, Anna J., McCartney, Daniel L., Campbell, Archie, Walker, Rosie M., Howard, David M., Ritchie, Craig W., Horvath, Steve, Hayward, Caroline, McIntosh, Andrew M., Porteous, David J., Deary, Ian J., Evans, Kathryn L., Marioni, Riccardo E.·2020·Clinical Epigenetics
DOI 10.1186/s13148-020-00905-6PMC PMC7394682

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Abstract

Background: Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five ‘epigenetic clocks’ which provide an index of how much an individual’s biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual’s biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries ( n ≤ 9537, Generation Scotland: Scottish Family Health Study). Results: DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. Conclusions: Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.

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  • All three DNAm measures have evidence for validity as biomarkers of aging, including association with aging-related morbidity and mortality and with exposures associated with shortened healthy lifespan.

    “All three measures have evidence for validity as biomarkers of aging, in particular, evidence of association with aging-related morbidity and mortality and with exposures associated with shortened healthy lifespan24,29,30.”

    From Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial (2023) · cites this paper as [30]

    The Discussion reports disease-incidence associations for DNAm GrimAge, DunedinPoAm and DNAm PhenoAge, and the Results associate these measures with smoking or deprivation. But the Results on all-cause mortality identify DNAm GrimAge alone; this paper does not establish a mortality association for all three measures. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The methods proposed to quantify biological aging analyzed in this study are predictive of aging-related health decline and mortality.

    “The methods proposed to quantify biological aging analyzed in this study are predictive of aging-related health decline and mortality.”

    From Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial (2023) · cites this paper as [30]

    The Conclusions report that epigenetic measures of ageing can predict the incidence of common diseases. However, the Results section 'Associations with all-cause mortality' finds that DNAm GrimAge alone was associated with mortality after adjustment, so the claim overgeneralizes the mortality finding to the methods analyzed as a group. (LLM, conf=0.85)

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Research works printed but not linked: 36

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Metadata

Authors
Hillary, R. F., Stevenson, A. J., McCartney, D. L., Campbell, A., Walker, R. M., Howard, D. M., Ritchie, C. W., Horvath, S., Hayward, C., McIntosh, A. M., Porteous, D. J., Deary, I. J., Evans, K. L., & Marioni, R. E.
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2020-07-31
Volume
12
Issue
1
ISSN
  • 1868-7075
  • 1868-7083
DOI
10.1186/s13148-020-00905-6
PMC
PMC7394682
Cited by
209
References
16
Language
en
Licence
Funders
  • Chief Scientist Office, Scottish Government Health and Social Care Directorate
  • Scottish Funding Council
  • Medical Research Council
  • Brain and Behavior Research Foundation
  • Wellcome Trust
  • Horizon 2020
  • Alzheimer’s Research UK

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