Biological Age Acceleration Measured By DunedinPACE Associates Most Consistently With Cognitive Decline In Elderly Individuals
Research Summary
An observational cohort analysis that asks which epigenetic clocks, built from DNA methylation in blood, best match cognitive performance and cognitive change in older adults. It compares 14 clocks from five development generations, plus a methylation-based estimate of telomere length. The paper is a preprint and has not been peer reviewed.
Who Or What Was Studied?
Up to 1,014 older adults (60-85 years at baseline) from the Berlin Aging Study II (BASE-II) with matched DNA methylation and cognitive data. Methylation was measured at two time points and nine cognitive tests at three time points (2013-2015, 2018-2020 and 2022-2023). Frailty was used as a non-cognitive comparison outcome. Models were adjusted for sex, age and genetic and methylation background factors.
What Did The Research Show?
- At baseline there were 14 associations that survived correction for multiple testing; 7 of them involved DunedinPACE, a clock that estimates the pace of biological ageing. DunedinPACE showed at least nominal association with 9 of 12 cognitive measures.
- In the longitudinal analysis, faster ageing by DunedinPACE was linked to steeper decline in five tests, including figural analogies (p = 9.84E-05) and the digit symbol substitution test (p = 1.37E-04). The SystemsAge clocks, especially Inflammation SystemsAge, came second.
- First-generation clocks (Horvath, Hannum), the fourth-generation “causal” clocks and methylation-estimated telomere length showed no noteworthy associations with cognition.
- All significant associations pointed the same way: better test scores went with slower biological ageing. No meaningful differences between men and women were found.
- DunedinPACE was also most strongly linked to frailty (p = 1.8×10-7 at follow-up).
Limitations And Interpretation
- A preprint that has not been certified by peer review.
- Observational data: the associations do not show that faster epigenetic ageing causes cognitive decline. No treatment, including rapamycin, was tested.
- Clocks were measured in blood, which only partly reflects ageing in the brain. At the follow-up time point, no cross-sectional association survived multiple-testing correction.
- Participants were older, mostly Northern European adults from Berlin, so the results may not apply to younger people or other populations.
Summary prepared from the published paper (abstract and full text where accessible). This is not medical advice — always consult the original publication.