© K. Link / Max-Planck-Institut für Biologie des Alterns
The researchers were able to show that Trametinib alone extends the lifespan of mice by 5-10%, while Rapamycin alone increases lifespan by 15-20%. Together, the drugs have a combinatorial effect that extends the life of the mice by around 30%.
The combination therapy also had positive effects on the health of the mice in old age. Less chronic inflammation was observed in the tissue and brain of the treated mice compared to untreated mice, and the onset and development of cancer was delayed.
Rapamycin and Trametinib are drugs used in cancer therapy that act on different points in the Ras/Insulin/TOR network, which plays a central role in ageing. Rapamycin is a potent geroprotector known to prolong the lifespan of animals. Geroprotectors are drugs that slow down the ageing process and extend lifespan. Trametinib acts on the Ras/MEK/ERK signalling pathway. It was not previously known whether Trametinib could extend the lifespan of mice, although previous studies in flies indicated that it might.
Although Rapamycin and Trametinib act on the same network, the combination achieves novel effects that are probably not solely due to an increase in dose. An analysis of gene expression in various tissues shows that the combination of the drugs influences the activity of the genes differently than is achieved by administering the drugs individually. There are specific changes in gene activity that are only caused by the combination of the two drugs.
The researchers plan to determine the optimal dose and route of administration of Trametinib to maximise the health and life-prolonging effects while minimising unwanted side effects. As Trametinib is already approved for human use, it is possible to test it in clinical trials.
"Trametinib, especially in combination with Rapamycin, is a good candidate to be tested in clinical trials as a geroprotector. We hope that our results will be taken up by others and tested in humans. Our focus is on optimising the use of Trametinib in animal models," explains Sebastian Grönke.
The research for this study was conducted at the Max Planck Institute for Biology of Ageing with funding from the European Research Council and co-funded by the CECAD Cluster of Excellence for Ageing Research at the University of Cologne.
Original publication:
Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, and Linda Partridge
The geroprotectors Trametinib and Rapamycin combine additively to extend mouse healthspan and lifespan
Nature Aging, 28 May, 2025
https://www.nature.com/articles/s43587-025-00876-4
Scientific contact:
Dr. Sebastian Grönke
Sebastian.Groenke[at]age.mpg.de
Max Planck Institute for Biology of Ageing, Cologne
Press and public relations:
Dr Maren Berghoff
Max Planck Institute for Biology of Ageing, Cologne
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About the Max Planck Institute for Biology of Ageing
The Max Planck Institute for Biology of Ageing conducts research into the natural ageing process with the long-term goal of paving the way for better health during the ageing process in humans. It is an institute within the Max Planck Society, which is one of the most successful research organisations in Germany. Since its foundation in 2008, the institute has been an integral part of the CECAD Cluster of Excellence for Ageing Research at the University of Cologne.