Jena/Kiel. DNA methylation data provide extremely accurate age predictors, but so far, little is known about the dynamics of this epigenomic biomarker over the course of life. A team of researchers from the Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), the Jena University Hospital (UKJ), and Christian-Albrecht University of Kiel (CAU) led by Dr. Maja Olecka, Dr. Alena van Bömmel, Prof. Christoph Kaleta, Dr. Christiane Frahm, and Prof. Steve Hoffmann has now made a groundbreaking discovery significantly contributing to narrowing this knowledge gap. The bioinformaticians investigated the epigenetic patterns (methylation trajectories) of the male mouse colon at different stages of aging.
In addition to the continuous DNA methylation changes observed during aging, they noted significant hypermethylation events at distinct life stages. According to the study published in Nature Communications, two key waves of epigenetic modifications take place; during the shift from early to middle age (3-9 months) and middle to late age (15-24 months). The life of rodents can thus be divided into three epigenetic stages.
The findings provide a new perspective on the dynamics of aging. "At least in the colon, the aging can no longer be regarded solely as a continuous accumulation of changes occurring during life. The identification of sudden methylation changes suggests that switch-like mechanisms also contribute to aging," explains Dr. Alena van Bömmel, one of the two lead authors. Her colleague Dr. Maja Olecka adds: “Importantly, nonlinear methylation changes are likely to impact the organ function. Genes affected by sudden changes at both DNA methylation and gene expression level are important players in various aspects of colon health and function like intestinal barrier, colon cancer or enteric nervous system”.
The research team also developed a clock-like classifier called STageR (STage of aging estimatoR), which can be used to predict the epigenetic stage of life in mice accurately. STageR differs from existing epigenetic clocks in that it is based on nonlinearly modified DNA regions and is not restricted to a fixed set of predictors. STageR thus expands the toolkit of machine learning models used in aging research. The accuracy of STageR has been confirmed in a separate strain of mice and on publicly available data.
The next steps of this exciting research project are already in sight: "The discovery of nonlinear methylation trajectories is a thrilling starting point for a new line of research. For example, we want to check whether the same phenomenon takes place in other tissues," explains Steve Hoffmann.
The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) – upon its inauguration in 2004 – was the first German research organization dedicated to research on the process of aging. Around 350 employees from around 40 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit
www.leibniz-fli.de.
The Leibniz Association connects 97 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 basic and applied research, including in the interdisciplinary Leibniz Research Alliances, maintain scientific infrastructure, and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer, particularly with the Leibniz research museums. It advises and informs policymakers, science, industry, and the general public. Leibniz institutions collaborate intensively with universities – including in the form of Leibniz ScienceCampi – as well as with industry and other partners at home and abroad. They are subject to a transparent, independent evaluation procedure. Because of their importance for the country as a whole, the Leibniz Association Institutes are funded jointly by Germany’s central and regional governments. The Leibniz Institutes employ around 20,500 people, including 11,500 researchers. The financial volume amounts to 2 billion euros. For more information:
www.leibniz-gemeinschaft.de/en/.