The emergence of epigenetic predictors was a pivotal moment in geroscience, propelling the measurement and concept of biological aging into a quantitative era. However, while current epigenetic clocks have shown strong predictive power, they do not reflect the underlying biological mechanisms driving methylation changes with age. Consequently, biological interpretation of their estimates is limited. Furthermore, our findings suggest that clocks trained on chronological age are confounded by non-age-related phenomena.
Addressing the limitations of existing epigenetic clocks
To address these limitations, we developed a probabilistic model that describes methylation transitions at the cellular level. Our approach reveals two measurable components, acceleration and bias, that directly relate to perturbations of the underlying cellular dynamics. Acceleration is the proportional increase in the speed of methylation transitions across CpG sites in the DNA, whereas bias is the degree of global change in methylation affecting all CpG sites uniformly. Using data from 7,028 participants from the Generation Scotland study, we found the acceleration parameter to be associated with physiological traits known to impact healthy aging. Furthermore, a genome-wide association study of age acceleration identified four genomic loci previously linked with aging.
Dr Tamir Chandra has been a Principal Investigator at the Institute of Genetics and Cancer at the University of Edinburgh since 2016. His group studies aging and disease from a systems biology perspective. Previously, Tamir Chandra conducted postdoctoral research at the Wellcome Sanger Institute and the Babraham Institute, Cambridge, UK.
Title of the talk: Why does methylation change with age?
When: Thursday, April 27, 2023, 4 p.m.
Where: Seminar room „Nucleus“, main building (FLI 1), Beutenbergstraße 11, Jena
Host: Dario Valenzano (Group Leader: Evolutionary Biology / Microbiome-Host Interactions in Aging)
The seminar will take place as a hybrid event. Access information will be shared prior to the seminar. For external guests: Please email Franziska.Baum@leibniz-fli.de for details.