scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood

Marc Jan Bonder (), Stephen J. Clark (), Felix Krueger, Siyuan Luo, João Agostinho de Sousa, Aida M. Hashtroud, Thomas M. Stubbs, Anne-Katrien Stark, Steffen Rulands, Oliver Stegle, Wolf Reik () and Ferdinand von Meyenn ()
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Marc Jan Bonder: German Cancer Research Center
Stephen J. Clark: Cambridge Institute of Science
Felix Krueger: Cambridge Institute of Science
Siyuan Luo: ETH Zurich
João Agostinho de Sousa: ETH Zurich
Aida M. Hashtroud: Max Planck Institute for the Physics of Complex Systems
Thomas M. Stubbs: The Babraham Institute
Anne-Katrien Stark: The Babraham Institute
Steffen Rulands: Max Planck Institute for the Physics of Complex Systems
Oliver Stegle: German Cancer Research Center
Wolf Reik: Cambridge Institute of Science
Ferdinand von Meyenn: ETH Zurich

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51833-5

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