Epigenetic Clock: Future of Hypertension Prediction?

HomeHypertensionVol. 80, No. 8Epigenetic Clock: Future of Hypertension Prediction? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBEpigenetic Clock: Future of Hypertension Prediction? Xiao-Man Wang, He-Ping Wang, Hou-Zao Chen and De-Pei Liu Xiao-Man WangXiao-Man Wang https://orcid.org/0000-0002-7833-6108 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China (X.-M.W., H.-P.W., H.-Z.C., D.-P.L.). *X.-M. Wang and H.-P. Wang contributed equally. Search for more papers by this author , He-Ping WangHe-Ping Wang State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China (X.-M.W., H.-P.W., H.-Z.C., D.-P.L.). *X.-M. Wang and H.-P. Wang contributed equally. Search for more papers by this author , Hou-Zao ChenHou-Zao Chen Correspondence to: De-Pei Liu, State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao, Beijing, China 100005, Email E-mail Address: [email protected] https://orcid.org/0000-0001-6805-3182 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China (X.-M.W., H.-P.W., H.-Z.C., D.-P.L.). Medical Epigenetics Research Center, Chinese Academy of Medical Sciences, Beijing, China (H.-Z.C., D.-P.L.). Search for more papers by this author and De-Pei LiuDe-Pei Liu Hou-Zao Chen, State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao, Beijing, China 100005, Email E-mail Address: [email protected] https://orcid.org/0000-0002-2636-4297 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China (X.-M.W., H.-P.W., H.-Z.C., D.-P.L.). Medical Epigenetics Research Center, Chinese Academy of Medical Sciences, Beijing, China (H.-Z.C., D.-P.L.). Haihe Laboratory of Cell Ecosystem, Tianjin, China (D.-P.L.). Search for more papers by this author Originally published20 Jul 2023https://doi.org/10.1161/HYPERTENSIONAHA.123.21197Hypertension. 2023;80:1569–1571In the current issue of Hypertension, Jacob et al1 revealed the intriguing associations between hypertension and blood DNA methylation, advancing our understanding of the epigenetic clock in capturing essential features of age-related physiological changes and disease risk (Figure). They present a racially diverse, prospective cohort of nearly 4500 women who were aged between 35 and 74 years from 2003 to 2009. At the baseline, women were categorized as hypertensive if they had elevated blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) or were taking antihypertensive medication. New cases of hypertension throughout follow-up were detected via self-report on annual health questionnaires. Three biological age metrics, including an estimator of aging rates (DunedinPACE) and 2 estimators of epigenetic age acceleration (PhenoAgeAccel, GrimAgeAccel), were defined based on previously published epigenetic clocks,2–4 and were measured using DNA methylation information derived from whole blood samples at the baseline. The authors conclude that DNA methylation-based biological age metrics significantly increased before hypertension diagnosis and remain persistently elevated in the years following clinical diagnosis and therapy.Download figureDownload PowerPointFigure. Omics strategies for hypertension prediction. DNA methylation-based epigenetic ages in the study showed strong statistical power to predict the incidence of hypertension in a large cohort of women (upper). Integrated age metrics using multi-omics data may have considerable potential to improve the accuracy and precision of hypertension prediction in the future (bottom).The study examines the direct relationships between epigenetic clocks and incident hypertension by conducting prospective cohorts, filling the lack of prospective evidence, particularly in the field of hypertension in women. Two interesting findings were highlighted. On the one hand, women with higher biological age at baseline are more prone to develop incident hypertension in the following years. The findings suggest that biological age could be a potential risk factor for hypertension, aiding in early intervention and prevention. Personalized prevention strategies for hypertension could also be developed based on an individual’s biological age. On the other hand, methylation-based biological age metrics remain elevated even after effective medication. The persistently increasing epigenetic age metrics even in the context of successful treatment and under-controlled blood pressure reflect the fact that epigenetic alterations may profile the comprehensive status of hypertension-induced molecular alterations. Thus, preventing harmful epigenetic changes caused by unhealthy lifestyles and damaging environmental factors5 may be more critical for hypertension treatment than just controlling blood pressure.Hypertension is typically diagnosed through the measurements of blood pressure, while well-established risk factors for the early prediction of hypertension remain complicated and unclear. Accumulating research has emerged to investigate various targets, including proteins,6 circular RNAs,7 and metabolites,8 which could potentially be used in the new prognosis, diagnosis, and therapy of hypertension. Jacob et al revealed that DNA methylation-based biological age metrics are prominently associated with hypertension, providing a new door for the discovery of hypertensive targets from the epigenetic perspective. Additionally, they have reported that biological age metrics have stronger associations with risk factors of cardiovascular diseases than with blood pressure alone. Specifically, significant positive correlations were observed between systolic blood pressure and biological age metrics (PhenoAgeAccel and GrimAgeAccel) when using minimally adjusted models, but these correlations were absent when adjusting for well-known risk factors of cardiovascular diseases. The independent relationships between biological age metrics and blood pressure further suggested that biological age metrics with the combination of blood pressure measurements could construct more effective predictive tools for hypertension events.Hypertension is the primary hazard factor for cardiovascular illness and premature death among females worldwide.9 Nevertheless, there is a crucial insufficiency of understanding regarding the gender-specific mechanisms of the disease. Additionally, risk factors for hypertension and cardiovascular illness that are exceptional to women are inadequately recognized in clinical recommendations.10 The study is based on a large cohort of 4419 women, and female-specific risk factors (ie, menopause status) were included in the model testing. This assessment may contribute to the limited gender-specific clinical diagnosis and treatment.The main strengths of the study by Jacob et al, include the use of a large cohort of women, the application of multiple DNA methylation-based biological age metrics, and the combination of both prospective and case-control analyses. These comprehensive designs provide strong statistical power and allow to adjustment of multiple confounding factors to draw meaningful conclusions. The study is limited by the mere use of baseline DNA methylation data to calculate biological age metrics. It would be interesting to investigate how changes in DNA methylation over time relate to hypertension incidence and progression. Given that multi-omics evaluations of aging have the potential to enhance the resolution of exploring aging-related diseases,11,12 multi-omics studies are strongly recommended to systematically understand the associations between hypertension and age (Figure).In conclusion, the findings of Jacob and colleagues provide new insights into the cross-sectional and prospective links between DNA methylation-based biological age and hypertension in a large cohort of women, indicating that biological age as one of risk factors may assist in early intervention and prevention. The success of epigenetic ages in predicting incident hypertension emphasizes the importance of elucidating epigenetic molecular pathways in hypertension. Moreover, deciphering the associations between biological ages and hypertension suggested other illnesses with abnormal blood pressure should consider the potential role of epigenetic ages in clinical diagnosis. While epigenetic clocks in blood represent a small step towards the application of biological ages for improving early prevention of hypertension, there is still much to learn and refine regarding the potential applications of biological ages through more comprehensive omics methods.ARTICLE INFORMATIONSources of FundingThis work was supported by grants from the National Key Research and Development Project of China (2020YFC2008003), the National Natural Science Foundation of China (grant numbers: 92149305 and 82225007, 82030017), and National High Level Hospital Clinical Research Funding (grant numbers: 2022-PUMCH-C-008 and 2022-PUMCH-C-014).Disclosures None.Footnotes*X.-M. Wang and H.-P. Wang contributed equally.For Sources of Funding and Disclosures, see page 1571.The opinions expressed in this article are not necessarily those of the editors nor the American Heart Association.Correspondence to: De-Pei Liu, State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao, Beijing, China 100005, Email liudp@pumc.edu.cnHou-Zao Chen, State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao, Beijing, China 100005, Email chenhouzao@ibms.cams.cnREFERENCES1. Kresovich JK, Sandler DP, Taylor JA. 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Measuring biological age using omics data.Nat Rev Genet. 2022; 23:715–727. doi: 10.1038/s41576-022-00511-7CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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