Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age

Jiménez-Balado J, Giralt-Steinhauer E, Fernández-Pérez I, Rey L et al. Biology (Basel). 2022 Dec 24;12(1):33. doi: 10.3390/biology12010033. PMID: 36671726; PMCID: PMC9855342.


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.

Funding: This work was supported by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III with the grants “Registro BASICMAR” Funding for Research in Health (PI051737), “GWALA project” from Fondos de Investigación Sanitaria ISC III (PI10/02064), (PI12/01238), (PI15/00451), (PI18/00022), (PI21/00593); Fondos FEDER/EDRF Spanish stroke research network INVICTUS+ (RD16/0019/0002) and Grant “RICORS-ICTUS” (RD21/0006/0021) funded by Instituto de Salud Carlos III (ISCIII) and by the European Union NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Additional support provided by Recercaixa’13 (JJ086116). E.G.-S. received a Juan Rodés research contract (JR18/00004—Spain’s Ministry of Health-Instituto de Salud Carlos III).