idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
Epigenetic clocks are important tools in modern aging research. Typically, they use characteristic DNA methylation patterns in the genome to precisely predict a person's age and infer conclusions about the individual’s biological aging processes. However, why this works so well and what biological mechanisms are behind it remain unclear. Researchers at the Leibniz Institute on Aging (FLI) have investigated the basis of established epigenetic clocks and developed a new model, The TFMethyl clock combines predictive accuracy with improved biological interpretability. The study provides new insights into molecular aging processes and opens new possibilities for research into age-related diseases
Jena. A person’s biological age does not always correspond to their chronological age, because lifestyle, environmental factors, or diseases can accelerate or even slow down the aging process. To make these differences measurable, so-called epigenetic clocks have been used worldwide for several years. Many of them rely on age-related changes in DNA methylation—chemical marks on DNA that can influence how genes are regulated.
Today, epigenetic clocks are among the most important biomarkers in aging research. They are used to investigate aging processes, better understand age-related diseases, and evaluate the effectiveness of potential anti-aging interventions. However, despite their high accuracy, the crucial question of which biological processes these clocks reflect has remained unanswered until now.
Taking a look inside the black box of epigenetic clocks
To close this knowledge gap, researchers at the Leibniz Institute on Aging—Fritz Lipmann Institute (FLI) in Jena, together with international partners from the Hebrew University of Jerusalem, the University of Edinburgh, and Queen Mary University of London, systematically investigated the DNA methylation sites of established epigenetic clocks and their regulatory function. The focus was on the binding sites of transcription factors that turn genes on or off, thereby controlling central processes of gene regulation. The study results have now been published in the journal Nucleic Acids Research.
“Epigenetic clocks have been providing impressively precise chronological age predictions. Nevertheless, surprisingly little is known about the biological mechanisms underlying these predictions,” explains Tushar Patel, first author of the study. The systematic analysis of DNA methylation sites used by most clock models revealed that many methylation sites do not lie within experimentally verified transcription factor binding sites.
“We therefore asked whether biological clocks could be improved by building them from regions of the genome that directly influence gene expression,” adds Steve Hoffmann, co-corresponding author of the study.
With this approach, the researchers identified a smaller group of regulatory DNA methylation sites that are closely enriched for aging processes. These include, among others, signaling pathways involved in interleukin-1β production and fatty acid metabolism. This points to molecular signaling pathways that may directly contribute to biological aging.
“Our model is one of the most accurate developed so far. More importantly, unlike other epigenetic clocks, it offers clues about the biological mechanisms that may directly shape how we age,” emphasizes Alena van Bömmel, the study’s last co-corresponding author, who has recently been appointed to the professorship of Neuroepigenetics and Data Science at the Ludwig-Maximilians University of Munich.
New epigenetic clock combines accuracy and interpretability
Based on these findings, the team developed a new epigenetic clock, the TFMethyl Clock. Unlike conventional models, this clock specifically considers DNA methylation sites that are both age-dependent and located within transcription factor binding sites. The approach was supplemented with new data-processing methods that cluster biologically similar methylation patterns. Overall, these strategies reduced confounding factors and further improved predictive performance and robustness.
The new clock achieved predictive accuracy comparable to established models and, in some cases, outperformed them. At the same time, it provides significantly deeper insights into the biological processes underlying the aging signatures and into the molecular networks to which they are connected. For example, the researchers found evidence of the involvement of signaling pathways associated with, among other things, the production of the inflammatory mediator interleukin-1β and fatty acid metabolism. Furthermore, about three-quarters of the target genes identified by the model exhibited age-dependent changes in gene activity—an indication that the selected markers do indeed reflect functionally relevant aging processes.
From biomarkers to tools in aging research
The study thus not only provides an improved method for age determination but also opens up new possibilities for systematically investigating the biological mechanisms of aging. In the long term, more biologically interpretable epigenetic clocks could help identify the molecular causes of age-related changes more precisely and inform the development of new approaches to the prevention and treatment of age-related diseases.
“In the future, epigenetic clocks could be much more than just precise biomarkers. They can help us understand which regulatory networks are involved in the aging process—and thus provide new avenues for research on aging,” the researchers said.
Publication
Enhancing the performance and interpretability of epigenetic clocks. Tushar Patel, Robert Schwarz, Konstantin Riege, Miri Varshavsky, Anne Richmond, Riccardo E Marioni, Hans A Kestler, Tommy Kaplan, Steve Hoffmann, Alena van Bömmel. Nucleic Acids Research, Volume 54, Issue 13, 22 July 2026, gkag661, https://doi.org/10.1093/nar/gkag661
https://academic.oup.com/nar/article/54/13/gkag661/8725950
Contact
Dr. Kerstin Wagner
Press & Public Relations
Phone: 03641-656378, Email: presse@leibniz-fli.de
###
Background
The Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) in Jena is a federal and state government-funded research institute and member of the Leibniz Association (Leibniz-Gemeinschaft). FLI conducts internationally recognized, high-impact research on the biology of aging at the molecular, cellular, and systems levels. Scientists from around 40 countries investigate the mechanisms of aging to uncover its root causes and pave the way for strategies that promote healthy aging. Further information: http://www.leibniz-fli.de.
The Leibniz Association connects 96 independent research institutions that range in focus from natural, engineering, and environmental sciences to economics, spatial, and social sciences and the humanities.
Leibniz Institutes address issues of social, economic, and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services.
The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz institutions collaborate intensively with universities – in the form of “Leibniz ScienceCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad.
They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the importance of the institutions for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 21,400 individuals, including 12,170 researchers. The entire budget of all the institutes is approximately 2,3 billion Euros. For more information: http://www.leibniz-gemeinschaft.de/en/.
Enhancing the performance and interpretability of epigenetic clocks. Tushar Patel, Robert Schwarz, Konstantin Riege, Miri Varshavsky, Anne Richmond, Riccardo E Marioni, Hans A Kestler, Tommy Kaplan, Steve Hoffmann, Alena van Bömmel. Nucleic Acids Research, Volume 54, Issue 13, 22 July 2026, gkag661, https://doi.org/10.1093/nar/gkag661
https://academic.oup.com/nar/article/54/13/gkag661/8725950
Epigenetic clocks determine biological age based on DNA methylation patterns. The new TFMethyl Clock ...
Copyright: (Image: FLI / Tushar Patel, AI-generated with ChatGPT)
FLI Press release (pdf)
Merkmale dieser Pressemitteilung:
Journalisten, Wissenschaftler, jedermann
Biologie, Chemie, Ernährung / Gesundheit / Pflege, Medizin
überregional
Forschungsergebnisse, Wissenschaftliche Publikationen
Englisch
Epigenetic clocks determine biological age based on DNA methylation patterns. The new TFMethyl Clock ...
Copyright: (Image: FLI / Tushar Patel, AI-generated with ChatGPT)
Sie können Suchbegriffe mit und, oder und / oder nicht verknüpfen, z. B. Philo nicht logie.
Verknüpfungen können Sie mit Klammern voneinander trennen, z. B. (Philo nicht logie) oder (Psycho und logie).
Zusammenhängende Worte werden als Wortgruppe gesucht, wenn Sie sie in Anführungsstriche setzen, z. B. „Bundesrepublik Deutschland“.
Die Erweiterte Suche können Sie auch nutzen, ohne Suchbegriffe einzugeben. Sie orientiert sich dann an den Kriterien, die Sie ausgewählt haben (z. B. nach dem Land oder dem Sachgebiet).
Haben Sie in einer Kategorie kein Kriterium ausgewählt, wird die gesamte Kategorie durchsucht (z.B. alle Sachgebiete oder alle Länder).
