Trametinib Modestly Extends Healthy Life Spans in Flies

Researchers have found that the MEK inhibitor trametinib, used as a cancer treatment, modestly extends life in flies. This is of interest for researchers involved in mapping the relationships between metabolism and natural variations in longevity, but otherwise not all that significant in the grand scheme of things. The plasticity of life span in response to drug treatments that alter the operation of metabolism is much greater in short-lived creatures, and it should be expected that a small extension of life such as this one would map to next to nothing in humans, even assuming that the underlying mechanism of action is in fact shared. I believe that efforts to develop drug treatments to slow aging in humans based on this sort of result are doomed to lengthy and expensive failure, or at best result in very marginal therapies that will do no more than add a couple of years to life expectancy - something that can already be achieved through exercise or calorie restriction.

Adult fruit flies given a cancer drug live 12% longer than average, according to a study researching healthy ageing. Trametinib is used to treat skin cancer and was chosen for its ability to inhibit Ras signalling as part of the Ras-Erk-ETS cell pathway. The role of Ras has been well characterised in cancer but it is also known to affect the ageing process. Previously, the DNA of yeast was changed to reduce Ras activity, which extended lifespan, so the team wanted to explore inhibitors of this pathway in an animal. "Our aim is to understand the mechanisms of ageing and alter the processes that lead to loss of function and to disease. We studied this molecular pathway in flies because they are reasonably complex and yet age more quickly than mammals. We were able to extend their lifespan both genetically and by using a cancer drug to target the Ras pathway, which provides us with the first evidence for the anti-ageing potential of drugs developed to dampen this pathway."

Female fruit flies were given trametinib as an additive in their food. A small dose of 1.56 µM, which is approximately equivalent to a daily dose of the drug in a human cancer patients, increased the fruit flies' average life expectancy by 8%. With a higher dose of 15.6 µM, the flies lived 12% longer on average. To test the anti-ageing properties of the drug in later life, fruit flies over 30 days old that had almost all stopped laying eggs were given the same moderate dose of 15.6 µM, and still had an increased life expectancy of 4%. Flies exposed continuously to the drug from an earlier stage in life lived longer than those who began dosing later in life, possibly indicating a cumulative effect of the drug. "Identifying the importance of the Ras-Erk-ETS pathway in animal ageing is a significant step on the way to developing treatments that delay the onset of ageing. The pathway is the same in humans as it is in flies and, because the Ras protein plays a key role in cancer, many small molecule drugs already exist, some of which have been approved for clinical use. With support from pharma, we can refine these molecules over the next 10-20 years to develop anti-ageing treatments which don't have the adverse effects of cancer drugs."



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