An international research team has demonstrated that combining two existing cancer drugs can extend lifespan in mice by approximately 30%, offering new insights into potential anti-aging therapies. The study, conducted at the Max Planck Institute for Biology of Ageing, found that trametinib and rapamycin together produce significantly greater longevity benefits than either drug administered alone.
Synergistic Effects Beyond Individual Drug Benefits
The researchers showed that trametinib alone extends mouse lifespan by 5-10%, while rapamycin alone increases lifespan by 15-20%. However, when combined, the drugs demonstrate a combinatorial effect that extends life by around 30%. This represents a substantial improvement over the additive effects of the individual treatments.
"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," the researchers noted. Gene expression analysis across various tissues revealed that the drug combination influences gene activity differently than administering the drugs individually, with specific changes occurring only when both drugs are used together.
Health Benefits Beyond Longevity
The combination therapy produced notable health improvements in aged mice beyond simple lifespan extension. Treated mice showed reduced chronic inflammation in both tissue and brain compared to untreated controls. Additionally, the onset and development of cancer was delayed in the treatment group.
Both drugs target different points within the Ras/Insulin/TOR signaling pathway, which plays a central role in aging processes. Rapamycin is already recognized as a potent geroprotector - a class of drugs that slow aging and extend lifespan in animals. While previous studies in flies suggested trametinib might have similar effects, this research represents the first demonstration of its lifespan-extending properties in mice.
Clinical Translation Potential
The research team is now working to determine optimal dosing and administration routes for trametinib to maximize health benefits while minimizing side effects. Importantly, trametinib is already approved for human use in cancer treatment, making clinical trials feasible.
"Trametinib, especially in combination with rapamycin, is a good candidate to be tested in clinical trials as a geroprotector," explained Sebastian Grönke, study author and biologist at the Max Planck Institute. "We hope that our results will be taken up by others and tested in humans. Our focus is on optimizing the use of trametinib in animal models."
Professor Dame Linda Partridge of UCL Institute of Healthy Ageing and Max Planck Institute for Biology of Ageing, co-senior author of the study, provided perspective on human applications: "While we do not expect a similar extension to human lifespans as we found in mice, we hope that the drugs we're investigating could help people to stay healthy and disease-free for longer late in life."
The research was funded by the European Research Council and co-funded by the CECAD Cluster of Excellence for Ageing Research at the University of Cologne. Further research in humans will be needed to determine how these drugs might benefit people and identify which populations could benefit most from such treatments.
