Scientists at IMB develop an epigenetic clock to measure ageing in frogs

The research groups of Prof. Christof Niehrs (Institute of Molecular Biology, IMB, Mainz, Germany) and Prof. Steve Horvath (University of California Los Angeles, USA) have created a DNA methylation-based “clock” that can be used to measure ageing in frogs—an important model organism used to study many fundamental aspects of biology. They discovered that despite the many biological differences between humans and frogs, both have surprisingly similar changes in DNA methylation with age. This “clock” will provide a useful tool to help researchers better understand the causes of ageing and develop new treatments for age-related diseases.

Ageing occurs in almost all organisms, from humans and mice to frogs and insects. To better understand why we age and to test new treatments against age-related diseases such as cardiovascular disease and cancer, scientists often study animals like mice, frogs and worms. These animals age much faster than humans, allowing studies to be completed in a few months or years, rather than decades. But is ageing in humans really the same as ageing in a frog?

One way to determine if ageing is similar across different species is to see whether the same molecular changes occur during ageing. In mammals, one of the most important age-related changes occurs in how our DNA is methylated. DNA methylation refers to small chemical groups (methyl groups) that are enzymatically attached to the bases of DNA. These methyl groups act like switches to turn genes on or off. Scientists have found that the on/off pattern of these “methylation switches” on the DNA naturally changes in a predictable way as we grow and age. Indeed, by analysing the on/off patterns of these methylation switches, scientists can determine the age of an individual with high accuracy. This pattern of changes in DNA methylation is known as the “epigenetic clock”.

But do these DNA methylation changes occur in other species as well, or are they unique to mammals? To investigate this, Prof. Niehrs and his colleagues analysed the DNA methylation patterns of African clawed frogs and western clawed frogs—both important model organisms used worldwide to study basic aspects of biology—ranging in age from 2 days to 19 years. The researchers discovered that DNA methylation in frogs also changes in a predictable way with age, just as it does in humans. In other words, frogs also have an “epigenetic clock”. Most interestingly, many of these age-related DNA methylation changes overlapped with those known to occur in humans. This indicates that despite the many biological differences between frogs and humans, the underlying DNA methylation changes that take place during ageing are remarkably similar in both species.

Based on this similarity, the researchers were able to construct the first epigenetic clock to measure age in frogs, as well as a combined epigenetic clock that measures age in both frogs and humans. Prof. Niehrs says, “The fact that age-related epigenetic changes in frogs and humans are so similar is highly significant because it suggests that the basic molecular processes that underlie ageing are the same. This means that any treatments that are found to be effective against age-related diseases in frogs may also be effective in humans.” The new frog epigenetic clock will also allow researchers who study ageing in frogs to more accurately test whether anti-ageing treatments are effective in slowing down ageing or preventing age-related diseases. This will be a key step towards designing new therapies that can help humans live longer and stay healthy into old age.

^{Further details}

^{Further information can be found at https://link.springer.com/article/10.1007/s11357-023-00840-3}

^{Christof Niehrs is a Scientific and Founding Director at the Institute of Molecular Biology (IMB). Further information about research in the Niehrs lab can be found at www.imb.de/niehrs.}

^{About the Institute of Molecular Biology gGmbH}

^{The Institute of Molecular Biology gGmbH (IMB) is a centre of excellence in the life sciences that was established in 2011 on the campus of Johannes Gutenberg University Mainz (JGU). Research at IMB focuses on the cutting-edge fields of epigenetics, genome stability, ageing and RNA biology. The institute is a prime example of successful collaboration between a private foundation and government: The Boehringer Ingelheim Foundation has committed 154 million euros to be disbursed from 2009 until 2027 to cover the operating costs of research at IMB. The State of Rhineland-Palatinate has provided approximately 50 million euros for the construction of a state-of-the-art building and is giving a further 52 million in core funding from 2020 until 2027. For more information about IMB, please visit: www.imb.de.}

^{About the Centre for Healthy Ageing}

^{The Centre for Healthy Ageing (CHA) is a virtual research centre launched in 2021 that brings together scientists in basic and clinical research from across Mainz that focus on ageing and age-related diseases. These findings should be used to promote healthy ageing and to find treatments that could prevent or cure age-related disease. For more information, please visit: www.cha-mainz.de.}

^{Boehringer Ingelheim Foundation}

^{The Boehringer Ingelheim Foundation is an independent, non-profit organization that is committed to the promotion of the medical, biological, chemical, and pharmaceutical sciences. It was established in 1977 by Hubertus Liebrecht (1931–1991), a member of the shareholder family of the Boehringer Ingelheim company. Through its Perspectives Programme Plus 3 and its Exploration Grants, the Foundation supports independent junior group leaders. It also endows the international Heinrich Wieland Prize, as well as awards for up-and-coming scientists in Germany. In addition, the Foundation funds institutional projects in Germany, such as the Institute of Molecular Biology (IMB), the department of life sciences at the University of Mainz, and the European Molecular Biology Laboratory (EMBL) in Heidelberg. www.bistiftung.de}

^{Press contact for further information}

^{Dr Ralf Dahm, Director of Scientific Management}

^{Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, 55128 Mainz, Germany}

^{Phone: +49 (0) 6131 39 21455, Email: press(at)imb.de}