Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood
Bibliographic record
Abstract
Introduction The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes. Methods DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath’s epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale (WAIS) in the late 20 s. Results The EpiAGE in adolescence, the early 20 s, and the late 20 s were positively correlated ( r = 0.34–0.47), suggesting that EpiAGE is a relatively stable characteristic of an individual. Further, a faster pace of aging between the measurements was positively correlated with EpiAGE at the end of the period ( r = 0.48–0.77) but negatively correlated with EpiAGE at the earlier time point ( r = −0.42 to −0.55), suggesting a compensatory mechanism where late matures might be catching up with the early matures. Finally, higher positive EpiAGE showed small (Adj R 2 = 0.03) but significant relationships with a higher positive brain age gap in all participants and lower full-scale IQ in young adult women in the late 20 s. Discussion We conclude that the EpiAGE is a relatively stable characteristic of an individual across adolescence and early adulthood, but that it shows only a small relationship with accelerated brain aging and a women-specific relationship with worse performance IQ.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".