Epigenetic clock explains white matter hyperintensity burden irrespective of chronological age

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...

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Detalles Bibliográficos
Autores: Jiménez-Balado, Joan, Giralt-Steinhauer, Eva, Fernández-Pérez, Isabel, Rey, Lucía, Cuadrado-Godia, Elisa, Ois Santiago, Angel Javier, Rodríguez-Campello, Ana, Soriano Tarraga, Carolina, Lazcano, Uxue, Macias-Gómez, Adrià, Suárez-Pérez, Antoni, Revert-Barberá, Anna, Estragués-Gázquez, Isabel, Beltrán Mármol, Marlyn Briggith, Medrano-Martorell, Santiago, Capellades, Jaume, Roquer, Jaume, Jiménez Conde, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/56298
Acceso en línea:http://hdl.handle.net/10230/56298
http://dx.doi.org/10.3390/biology12010033
Access Level:acceso abierto
Palabra clave:White matter hyperintensities
Cerebral small vessel disease
Epigenetics
DNA methylation
Biological age
Epigenetic clock
Descripción
Sumario: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.

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