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Accelerated Epigenetic Aging and Its Role in Brain Dynamics and Cognition in Young Adulthood

T. Jordánek, R. Mareček, A. Pačínková, L. Andrýsková, M. Brázdil, K. Marečková

. 2025 ; 46 (10) : e70261. [pub] -

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc25015162

Grant support
24-12183M Grantová Agentura České Republiky
NU20J-04-00022 Agentura Pro Zdravotnický Výzkum České Republiky
CEITEC 2020 Czech Ministry of Education, Youth and Sport
LM2023069 Czech Ministry of Education, Youth and Sport
LQ1601 Czech Ministry of Education, Youth and Sport
LX22NPO5107 Czech Ministry of Education, Youth and Sport
857560 HORIZON EUROPE Health

Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.

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$a Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.
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