Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 1;10(12):3094.
doi: 10.3390/biomedicines10123094.

The Blood DNA Methylation Clock GrimAge Is a Robust Surrogate for Airway Epithelia Aging

Ana I Hernandez Cordero  1 , Chen Xi Yang  1 , Xuan Li  1 , Julia Yang  1 , Tawimas Shaipanich  2 , Julie L MacIsaac  3 , David T S Lin  3 , Michael S Kobor  3 , Steve Horvath  4   5 , Shu Fan Paul Man  1   2 , Don D Sin  1   2 , Janice M Leung  1   2
Affiliations

The Blood DNA Methylation Clock GrimAge Is a Robust Surrogate for Airway Epithelia Aging

Ana I Hernandez Cordero et al. Biomedicines. .

Abstract

One key feature of Chronic Obstructive Pulmonary Disease (COPD) is that its prevalence increases exponentially with age. DNA methylation clocks have become powerful biomarkers to detect accelerated aging in a variety of diseases and can help prognose outcomes in severe COPD. This study investigated which DNA methylation clock could best reflect airway epigenetic age when used in more accessible blood samples. Our analyses showed that out of six DNA methylation clocks investigated, DNAmGrimAge demonstrated the strongest correlation and the smallest difference between the airway epithelium and blood. Our findings suggests that blood DNAmGrimAge accurately reflects airway epigenetic age of individuals and that its elevation is highly associated with COPD.

Keywords: COPD; airway epithelium; blood; epigenetic age.

PubMed Disclaimer

Conflict of interest statement

J.M.L. reports research grant funding (to institution) from Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, BC Lung Association and Genome BC, and a grant from AstraZeneca, outside of the submitted work. S.H. reports consulting fees from the non-profit organization, Epigenetic Clock Development Foundation, and royalty income from patents surrounding epigenetic clocks. D.D.S. declares payments from AstraZeneca, GSK, and Boehringer Ingelheim, outside of the submitted work. The remaining authors have nothing to disclose.

Figures

Figure 1
Figure 1
Difference between airway epithelial and blood epigenetic age. Bland–Altman Plots show the difference between the measurements (y-axis) and average values for the blood and airway epigenetic age (x-axis) for: (a) DNAmGrimAge; (b) DNAmAge (pan-tissue); (c) DNAmAgeHannum; (d) DNAmAgeSkinBlood; (e) DNAmPhenoAge; (f) DNAmTL. Blue dots: non-COPD. Red dots: COPD. Red dotted lines: standard deviation. Black horizontal line: average difference between blood and airway epigenetic age.
Figure 2
Figure 2
DNAmGrimAge age acceleration residuals in blood (a) and airway (a) samples and COPD. (a,b) show DNAmGrimAge age residuals based on COPD status (N = COPD negative, Y = COPD positive) (x-axis). The y-axis on the plots represents the residuals obtained from the regression of methylation age on the chronological age, body mass index, sex, and smoking status. Blood analysis was further adjusted for blood cell composition Significant p-values (p < 0.05) associated with the COPD status are shown inside the plots.
See this image and copyright information in PMC

References

    1. Khakban A., Sin D.D., FitzGerald J.M., McManus B.M., Ng R., Hollander Z., Sadatsafavi M. The Projected Epidemic of Chronic Obstructive Pulmonary Disease Hospitalizations over the Next 15 Years. A Population-based Perspective. Am. J. Respir. Crit. Care Med. 2017;195:287–291. doi: 10.1164/rccm.201606-1162PP. - DOI - PubMed
    1. Hernandez Cordero A.I., Yang C.X., Milne S., Li X., Hollander Z., Chen V., Ng R., Tebbutt S.J., Leung J.M., Sin D.D. Epigenetic Blood Biomarkers of Ageing and Mortality in COPD. Eur. Respir. J. 2021;58:2101890. doi: 10.1183/13993003.01890-2021. - DOI - PubMed
    1. Hernández Cordero A.I., Yang C.X., Yang J., Horvath S., Shaipanich T., MacIsaac J., Lin D.T.S., Kobor M.S., Guillemi S., Harris M., et al. Airway Aging and Methylation Disruptions in HIV-Associated Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2022;206:150–160. doi: 10.1164/rccm.202106-1440OC. - DOI - PMC - PubMed
    1. Hernandez Cordero A.I., Yang C.X., Obeidat M., Yang J., MacIsaac J., McEwen L., Lin D., Kobor M., Novak R., Hudson F., et al. DNA Methylation Is Associated with Airflow Obstruction in Patients Living with HIV. Thorax. 2021;76:448–455. doi: 10.1136/thoraxjnl-2020-215866. - DOI - PMC - PubMed
    1. Horvath S. DNA Methylation Age of Human Tissues and Cell Types. Genome. Biol. 2013;14:R115. doi: 10.1186/gb-2013-14-10-r115. - DOI - PMC - PubMed

LinkOut - more resources