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Nature of epigenetic aging from a single-cell perspective
Andrei E Tarkhov1,2, Thomas Lindstrom-Vautrin3, Sirui Zhang3
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. andrei@retro.bio.
Nature Aging
|May 9, 2024
Summary
Epigenetic aging involves both coordinated and random DNA methylation changes, impacting epigenetic clock accuracy. Understanding these dynamics offers insights into aging and longevity interventions.
Area of Science:
- Epigenetics and aging research
- Genomics and computational biology
Background:
- Epigenetic clocks, based on DNA methylation (DNAm), are robust age predictors.
- The precise mechanistic basis of what epigenetic clocks quantify remains unclear.
Purpose of the Study:
- To clarify the nature of epigenetic aging by comparing tissue and single-cell DNA methylation dynamics.
- To investigate the relationship between epigenetic aging and transcriptional patterns.
Main Methods:
- Juxtaposition of tissue and single-cell DNA methylation dynamics in mice during development and aging.
- Integration with single-cell RNA sequencing data within a multiomics dataset.
- Modeling of DNA methylation trajectories using stochastic processes.
Main Results:
- Epigenetic aging comprises co-regulated changes and a significant stochastic component.
- Stochastic epigenetic aging patterns are consistent with observed transcriptional dynamics.
- A novel single-cell algorithm identified coordinated and stochastic CpG clusters with transcriptomic links.
Conclusions:
- Epigenetic aging has both deterministic and stochastic elements, influencing epigenetic clock precision.
- Findings enhance understanding of epigenetic clock mechanisms.
- Identified patterns may offer targets for aging interventions and longevity research.
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