Biological Aging and Geroscience
Developing and validating biological aging measures across cohorts, trials, and clinical data
Past Work
My work in biological aging began with the use of epigenetic clocks to study life course exposures, reproduction, stress, and health in human populations. In a review for human biologists, I summarized how epigenetic clocks are constructed, what they appear to measure, and how they can be applied to questions in development, stress biology, life history, and epidemiology.
The Cebu Longitudinal Health and Nutrition Survey has been foundational to this work. It provided a setting for applying biological aging measures in a long-running, non-WEIRD cohort with rich developmental, reproductive, social, and molecular data.
Current Work
My current geroscience work focuses on developing, implementing, and validating measures of biological aging in cohorts, trials, and clinical datasets. In the CALERIE DNA methylation analysis, we found that long-term caloric restriction slowed DunedinPACE in healthy adults, providing experimental support for the idea that behavioral interventions can modify biological aging processes in humans.
I also lead and support multi-omic data resource curation for translational geroscience. In the CALERIE Genomic Data Resource, we described a multi-tissue, multi-omic resource with longitudinal DNA methylation, mRNA, small RNA, and genetic data from a randomized trial of caloric restriction.
Building from this work, I am Analysis Project Lead for FAST: Finding Aging biomarkers by Searching existing Trials, an ARPA-H supported initiative focused on identifying biomarkers of aging across existing human trials.
Future Work
I am interested in measures that move beyond any single omic layer. DNA methylation remains central to my work, but I increasingly view epigenetic clocks as part of a broader measurement problem involving clinical chemistry, inflammation, immune function, metabolomics, proteomics, and longitudinal health outcomes.
My goal is to help build biological aging measures that are interpretable, transportable across populations and study designs, and useful for testing interventions that aim to improve healthspan.
Selected References
Ryan CP. Epigenetic clocks: Theory and applications in human biology. American Journal of Human Biology. 2020.
Ryan CP, Corcoran DL, Banskota N, et al. The CALERIE Genomic Data Resource. Nature Aging. 2024.
Waziry R, Ryan CP, Corcoran DL, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging. 2023.