scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood
Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.
Authors
- Ferdinand von Meyenn (ORCID: https://orcid.org/0000-0001-9920-3075)
- Marc Jan Bonder (ORCID: https://orcid.org/0000-0002-8431-3180)
- Thomas M. Stubbs (ORCID: https://orcid.org/0000-0002-2990-7381)
- Wolf Reik (ORCID: https://orcid.org/0000-0003-0216-9881)
- Anne‐Katrien Stark (ORCID: https://orcid.org/0000-0001-6241-3909)
- Felix Krueger (ORCID: https://orcid.org/0000-0002-5513-3324)
- Aida M. Hashtroud
- Siyuan Luo (ORCID: https://orcid.org/0009-0007-6404-3244)
- Steffen Rulands (ORCID: https://orcid.org/0000-0001-6398-1553)
- João Agostinho de Sousa (ORCID: https://orcid.org/0000-0001-8124-6624)
- Oliver Stegle (ORCID: https://orcid.org/0000-0002-8818-7193)
- Stephen J. Clark (ORCID: https://orcid.org/0000-0002-6183-491X)
Institutions
- New England Biolabs (United States) (US)
- Babraham Institute (GB)
- University Medical Center Groningen (NL)
- Omron (Japan) (JP)
- German Cancer Research Center (DE)
- King's College London (GB)
- Heidelberg University (DE)
- Center for NanoScience (DE)
- Wellcome Sanger Institute (GB)
- ETH Zurich (CH)
- Oncode Institute (NL)
- Max Planck Institute for the Physics of Complex Systems (DE)
- European Molecular Biology Laboratory (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-31
- DOI
- https://doi.org/10.1038/s41467-024-51833-5
- Citations
- 14
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 3.27
Funders
- Wellcome Trust
- European Commission
- King's Health Partners
- Eidgenössische Technische Hochschule Zürich
- Biotechnology and Biological Sciences Research Council