Researchers from University College London and the Max Planck Institute for the Biology of Aging tested a combination of two anti-cancer drugs on mice and extended their life expectancy by 35%.
It is a combination of rapamycin and trametinib. It is noted that mice injected with these drugs showed significantly healthier aging, delayed tumor formation, lower levels of inflammation, and signs of improved brain and cardiovascular function.
«We do not expect the same increase in human life expectancy as we found in mice. But we hope that the drugs we are studying will help people stay healthy and get less sick in old age», — emphasized the study’s co-author, geneticist Linda Partridge.
At the beginning of the study, researchers sought to answer the question of whether the combination of two geroprotective drugs to provide a greater effect than the sum of their parts. Rapamycin was originally derived from soil bacteria from Easter Island. It was widely used to prevent organ rejection in patients after transplantation and consistently prolonged life in mice, even when administered in old age.
Trametinib was approved for the treatment of melanoma Although it prolonged the life of fruit flies, its effects in mammals were still unknown. To find out, researchers at the Max Planck Institute kept hundreds of mice on a diet that contained Rapamycin, trametinib, or a combination of both.
By itself Rapamycin increased the average life expectancy of mice by 17-18%. Trametinib, on the other hand, extended life expectancy by 7-16%. A mixture of these drugs increased the life expectancy of mice by 26-35%. The most pronounced effect was observed in female mice Maximum life expectancy also increased: by 32% in females and by 26% — in males.
As the researchers emphasize, it’s not just about life expectancy, but also about improving the health of rodents. Mice treated with both drugs were more active in old age and gained less weight, and showed a slower decline in heart function. They even had reduced brain inflammation and lower cancer rates.
«We found that the combination of rapamycin and trametinib has an additive effect on both life expectancy and health status. The combination significantly reduced tumors and inflammation compared to each drug alone», — notes the lead co-author of the study Sebastian Grönke.
Both drugs target a biological system known as the Ras/Insulin/TOR signaling network. This mechanism regulates growth and metabolism. It is involved in the aging process and is responsible for the onset of age-related diseases. Rapamycin inhibits mTORC1, a key protein complex in this network, while trametinib blocks MEK proteins further down the Ras pathway.
The researchers note that the effect of the drugs is likely to cause changes in gene expression that neither drug alone is capable of. The results of tissue analysis of mice treated with both drugs showed that the combination caused unusual shifts in gene activity. This was especially true for genes responsible for inflammation and immune system function.
The combination of the two drugs completely blocked the age-related changes in the brains of mice that provoked increased glucose uptake and was associated with cognitive decline. Markers of chronic inflammation were significantly reduced in the brain, kidneys, spleen, and muscles.
The treatment curbed the appearance of tumors. While almost 70% of male mice that did not take the drugs began to develop liver tumors in the second year of life, the number of tumors was significantly lower in those mice that took both drugs.
At the same time The combination did not increase the side effects already associated with either drug. While rapamycin alone caused increased blood sugar levels,Trametinib did not, and the combination did not enhance this effect. Previous clinical studies have shown that Rapamycin may have anti-aging effects, improving immune function in the elderly.
Source: ZMEScience
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