Heidi Ledford in Nature:
A cancer drug that boosts the lifespan of fruit flies is the latest addition to a small roster of compounds shown to lengthen life — although none has yet been proven in humans. Trametinib (Mekinist), which was developed by the London-based pharmaceutical firm GlaxoSmithKline, is already used to treat advanced melanoma. It extends the lifespan of adult fruit flies by about 12%, although the later in life the drug is started, the less effect it has, says Linda Partridge, a geneticist at University College London and the Max Planck Institute for Biology of Ageing in Cologne, Germany, who led the work. Her team’s research is reported on 25 June in Cell1. But Partridge cautions against rushing to take trametinib in search of a longer life. “That would be mad,” she says. “We just don’t know enough about the long-term consequences.”
Trametinib’s effects are connected to a biochemical pathway controlled by a family of proteins collectively called Ras which seem to be important to both cancer and ageing. They are activated when cells need to grow and proliferate, for example to replace damaged tissue. Mutations in the proteins are associated with cancer — which has led to a decades-long pursuit of drugs that target Ras. At the same time, Ras proteins are involved in other pathways that have been firmly linked to ageing. In yeast, deleting a gene for Ras extends lifespan2, notes Valter Longo, director of the University of Southern California’s Longevity Institute in Los Angeles. And Partridge’s team showed that trametinib’s benefits in fruit flies depended on suppressing a pathway regulated by Ras. Flies genetically modified to have this pathway permanently switched on did not live longer on trametinib.