Publication details

Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood

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Authors

MAREČKOVÁ Klára MENDES-SILVA Ana Paula MAREČEK Radek JORDÁNEK Tomáš PAČÍNKOVÁ Anna KLÁNOVÁ Jana GONCALVES Vanessa F NIKOLOVA Yuliya S

Year of publication 2026
Type Article in Periodical
Magazine / Source Human Brain mapping
MU Faculty or unit

Faculty of Medicine

Citation
web https://onlinelibrary.wiley.com/doi/10.1002/hbm.70447
Doi https://doi.org/10.1002/hbm.70447
Keywords dorsal attention network; functional impact score of mitochondrial variants (mtDNA FI score); general connectivity; language network; mitochondria dysfunction; young adulthood
Description Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature epigenetic aging in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact (FI) score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR 2 = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. Overall, we conclude that individuals with a greater mtDNA FI score might be at greater risk of experiencing worse attention to relevant linguistic inputs, greater difficulties with speech comprehension, and verbal working memory.
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