Wang, Yucheng and Grant, Olivia and Zhai, Xiaojun and McDonald-Maier, Klaus and Schalkwyk, Leonard (2023) Insights into ageing rates comparison across tissues from recalibrating cerebellum DNA methylation clock. GeroScience, 46 (1). pp. 39-56. DOI https://doi.org/10.1007/s11357-023-00871-w
Wang, Yucheng and Grant, Olivia and Zhai, Xiaojun and McDonald-Maier, Klaus and Schalkwyk, Leonard (2023) Insights into ageing rates comparison across tissues from recalibrating cerebellum DNA methylation clock. GeroScience, 46 (1). pp. 39-56. DOI https://doi.org/10.1007/s11357-023-00871-w
Wang, Yucheng and Grant, Olivia and Zhai, Xiaojun and McDonald-Maier, Klaus and Schalkwyk, Leonard (2023) Insights into ageing rates comparison across tissues from recalibrating cerebellum DNA methylation clock. GeroScience, 46 (1). pp. 39-56. DOI https://doi.org/10.1007/s11357-023-00871-w
Abstract
DNA methylation (DNAm)-based age clocks have been studied extensively as a biomarker of human ageing and a risk factor for age-related diseases. Despite different tissues having vastly different rates of proliferation, it is still largely unknown whether they age at different rates. It was previously reported that the cerebellum ages slowly; however, this claim was drawn from a single clock using a relatively small sample size and so warrants further investigation. We collected the largest cerebellum DNAm dataset (N = 752) to date. We found the respective epigenetic ages are all severely underestimated by six representative DNAm age clocks, with the underestimation effects more pronounced in the four clocks whose training datasets do not include brain-related tissues. We identified 613 age-associated CpGs in the cerebellum, which accounts for only 14.5% of the number found in the middle temporal gyrus from the same population (N = 404). From the 613 cerebellum age-associated CpGs, we built a highly accurate age prediction model for the cerebellum named CerebellumClockspecific (Pearson correlation=0.941, MAD=3.18 years). Ageing rate comparisons based on the two tissue-specific clocks constructed on the 201 overlapping age-associated CpGs support the cerebellum has younger DNAm age. Nevertheless, we built BrainCortexClock to prove a single DNAm clock is able to unbiasedly estimate DNAm ages of both cerebellum and cerebral cortex, when they are adequately and equally represented in the training dataset. Comparing ageing rates across tissues using DNA methylation multi-tissue clocks is flawed. The large underestimation of age prediction for cerebellums by previous clocks mainly reflects the improper usage of these age clocks. There exist strong and consistent ageing effects on the cerebellar methylome, and we suggest the smaller number of age-associated CpG sites in cerebellum is largely attributed to its extremely low average cell replication rates.
Item Type: | Article |
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Uncontrolled Keywords: | Ageing rate; Epigenetic clocks; Cerebellum; DNA methylation |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of Faculty of Science and Health > Computer Science and Electronic Engineering, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 26 Sep 2023 16:11 |
Last Modified: | 16 May 2024 21:55 |
URI: | http://repository.essex.ac.uk/id/eprint/35945 |
Available files
Filename: s11357-023-00871-w.pdf
Licence: Creative Commons: Attribution 4.0