According to a study, a combination of two cancer drugs, rapamycin and trametinib, can increase longevity in mice by 30%
The research, published in Nature Aging, showed that the combination therapy showed greater effects than the individual drugs, offering longevity and health benefits in old age. The results suggest that the drugs could be promising for combating age-related diseases and extending life.
Repurposing cancer drugs to tackle chronic conditions
Rapamycin and trametinib are drugs currently used in cancer therapy that act on different points in the body’s Ras/Insulin/TOR signalling 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 related Ras/MEK/ERK signalling pathway.
Previous research by the same group indicated that trametinib had the potential to increase longevity in flies.
In the latest study, the researchers gave mice either trametinib alone, rapamycin alone, both, or neither, with the drugs delivered in their food from six months of age onwards. They found that trametinib alone extends the lifespan of mice by 5-10%, while rapamycin alone increases lifespan by 15-20%. However, when used together, the drugs have a synergistic effect, increasing longevity by around 30%.
Additionally, the drugs positively improved the health of mice in old age. Mice receiving the combination treatment exhibited decreased age-related increases in brain glucose uptake and showed significant reductions in inflammation across multiple organs, including the brain, kidney, spleen, and muscle. Circulating levels of pro-inflammatory cytokines were also markedly reduced.
The combination therapy also reduced the occurrence of liver tumours in both sexes and spleen tumours in male mice, suggesting a protective effect against certain age-related cancers.
Co-lead author Professor Dame Linda Partridge (UCL Institute of Healthy Ageing and Max Planck Institute for Biology of Ageing) said: “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. Further research in humans in years to come will help us to elucidate how these drugs may be useful to people, and who might be able to benefit.”
Determining the optimal dose to maximise longevity
Rapamycin and trametinib act on the same network; however, the combination achieves effects that are probably not solely due to an increase in dose. An analysis of gene expression in various tissues sampled from the mice showed that the combination of the drugs influences the activity of the genes differently than when the drugs are administered individually. There are specific changes in gene activity that are only caused by the combination of the two drugs.
The researchers are focused on establishing the optimal dose and route of administration of trametinib to maximise health and longevity without unwanted side effects.
These findings suggest potential for repurposing these drugs as geroprotective therapies in humans, pending further research and clinical trials.
Co-lead author Dr Sebastian Grönke (Max Planck Institute for Biology of Ageing) said: “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.”
