Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age

• Published in: Biology (Basel, Switzerland) Vol. 12; no. 1; p. 33
• Main Authors: Jiménez-Balado, Joan, Giralt-Steinhauer, Eva, Fernández-Pérez, Isabel, Rey, Lucía, Cuadrado-Godia, Elisa, Ois, Ángel, Rodríguez-Campello, Ana, Soriano-Tárraga, Carolina, Lazcano, Uxue, Macias-Gómez, Adrià, Suárez-Pérez, Antoni, Revert, Anna, Estragués, Isabel, Beltrán-Mármol, Brigitte, Medrano-Martorell, Santiago, Capellades, Jaume, Roquer, Jaume, Jiménez-Conde, Jordi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-12-2022; MDPI
• Subjects: Age; Aging; biological age; Blood; cerebral small vessel disease; Dementia disorders; Disease; DNA methylation; epigenetic clock; Epigenetics; Etiology; Gene expression; Genomes; Hospitals; Hypertension; Ischemia; Magnetic resonance imaging; Medical imaging; Neuroimaging; Regression analysis; Risk factors; Stroke; Substantia alba; Variables; white matter hyperintensities; DNA methylation; cerebral small vessel disease; biological age; white matter hyperintensities; epigenetics; epigenetic clock
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12010033

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 cm
, Q1-Q3 = 4.05-18.8). After adjusting for potential confounders, we observed a significant effect of B-age
on WMH volume (β
= 0.023,
-value = 0.029) independently of C-age, which remained significant (β
= 0.021,
-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-age
. On the other hand, B-age
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.