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[Preprint]. 2024 Jun 25:rs.3.rs-4378855.
doi: 10.21203/rs.3.rs-4378855/v1.

Bidirectional relationship between epigenetic age and brain health events

Cyprien Rivier  1 , Natalia Szejko  2 , Daniela Renedo  1 , Santiago Clocchiatti-Tuozzo  1 , Shufan Huo  1 , Adam de Havenon  3 , Hongyu Zhao  4 , Thomas Gill  1 , Kevin Sheth  3 , Guido Falcone  4
Affiliations

Bidirectional relationship between epigenetic age and brain health events

Cyprien Rivier et al. Res Sq. .

Update in

Abstract

Chronological age offers an imperfect estimate of the molecular changes that occur with aging. Epigenetic age, which is derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. This study examines the bidirectional relationship between epigenetic age and the occurrence of brain health events (stroke, dementia, and late-life depression). Using data from the Health and Retirement Study, we analyzed blood samples from over 4,000 participants to determine how epigenetic age relates to past and future brain health events. Study participants with a prior brain health event prior to blood collection were 4% epigenetically older (beta 0.04, SE 0.01), suggesting that these conditions are associated with faster aging than that captured by chronological age. Furthermore, a one standard deviation increase in epigenetic age was associated with 70% higher odds of experiencing a brain health event in the next four years after blood collection (OR 1.70, 95%CI 1.16-2.50), indicating that epigenetic age is not just a consequence but also a predictor of poor brain health. Both results were replicated through Mendelian Randomization analyses, supporting their causal nature. Our findings support the utilization of epigenetic age as a useful biomarker to evaluate the role of interventions aimed at preventing and promoting recovery after a brain health event.

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Conflict of interest statement

Dr. de Havenon reports NIH/NINDS funding (K23NS105924, R01NS130189, UG3NS130228). Dr. de Havenon has received consultant fees from Novo Nordisk, royalty fees from UpToDate, and has equity in TitinKM and Certus.

Figures

Figure 1
Figure 1
Flowchart
Figure 2
Figure 2
Flowchart of Stage 1 genetic analyses
Figure 3
Figure 3
Flowchart of Stage 2 genetic analyses.
Figure 4
Figure 4. Associations between epigenetic age and brain health events (stroke, dementia, late-life depression).
A. Cross-sectional analysis: percentage of change in epigenetic ages following a brain health event after adjusting for chronological age, sex, race and ethnicity, hypertension, diabetes, smoking, BMI, history of heart attack, coronary artery disease, angina, or congestive heart failure. B. Longitudinal analysis: Odds Ratios of brain health events per one standard deviation increase in epigenetic age adjusting for chronological age, sex, and race and ethnicity.
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