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Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age
Joan Jiménez-Balado1, Eva Giralt-Steinhauer1, Isabel Fernández-Pérez1
1Neurovascular Research Group, Department of Neurology, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
Abstract:
In this manuscript we studied the relationship between WMH and biological age (B-age) in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively high median WMH volume (median = 8.8 cm3, Q1-Q3 = 4.05-18.8). After adjusting for potential confounders, we observed a significant effect of B-ageHannum on WMH volume (βHannum = 0.023, p-value = 0.029) independently of C-age, which remained significant (βC-age = 0.021, p-value = 0.036). Finally, we performed a mediation analysis, which allowed us to discover that 42.7% of the effect of C-age on WMH is mediated by B-ageHannum. On the other hand, B-ageHoarvath showed no significant associations with WMH after being adjusted for C-age. In conclusion, we show for the first time that biological age, measured through DNA methylation, contributes substantially to explain WMH volumetric burden irrespective of chronological age.
Insights
Biological age, determined by DNA methylation, significantly predicts white matter hyperintensities (WMH) volume in stroke patients, independent of chronological age. This epigenetic measure explains a substantial portion of WMH burden, offering new insights into stroke pathology.
Area of Science:
- Neuroscience
- Epigenetics
- Gerontology
Background:
- White matter hyperintensities (WMH) are common in acute stroke patients.
- Biological age (B-age), estimated via DNA methylation, may offer insights into age-related brain changes beyond chronological age (C-age).
Purpose of the Study:
- To investigate the association between B-age and WMH volume in acute stroke patients.
- To determine if B-age influences WMH independently of C-age.
Main Methods:
- Epigenetic data (DNA methylation) and magnetic resonance imaging (MRI) data were collected from 247 acute stroke patients.
- WMH volume was quantified using a semi-automated method.
- B-age was calculated using Hannum and Horvath epigenetic clocks; associations with WMH were analyzed using multiple linear regression, adjusting for C-age and other covariates.
Main Results:
- B-age calculated using the Hannum formula (B-ageHannum) was significantly associated with increased WMH volume, independent of C-age.
- B-ageHannum explained 42.7% of the effect of C-age on WMH volume.
- B-age calculated using the Horvath formula (B-ageHorvath) did not show a significant association with WMH volume after adjusting for C-age.
Conclusions:
- Epigenetic B-age (Hannum clock) is a significant predictor of WMH volume in acute stroke patients, irrespective of C-age.
- This study highlights the role of epigenetic aging in the development of WMH, a key marker of cerebrovascular damage.
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