Fruit Flies Live Longer With Combination Treatment

A combined drug cocktail of three drugs that are already being used as medical treatments have been used to extend the lifespan of fruit flies by 48%. The cocktail consists of: rapamycin which is an immune system regulator, lithium which is a mood stabiliser, and trametinib which is a cancer treatment.

"As life expectancies increase, we are also seeing an increase of age-related diseases so there is an urgent need to find ways to improve health in old age," said the study's co-lead author, Dr Jorge Castillo-Quan, who began the research at the UCL Institute of Healthy Ageing before moving to Joslin Diabetes Center, Harvard Medical School.

"Here, by studying fruit flies which age much more rapidly than people, we have found that a combination drug treatment targeting different cellular processes may be an effective way to slow down the ageing process."

Each of the three drugs act on different cellular signalling pathways that collectively form the nutrient sensing network, which is conserved across evolution from files and worms to humans, which adjusts what the body is doing in response to changes in nutrient levels; each drug acts on different protein of the network to slow the aging process and delay onset of age related death. 

Fruit flies were given doses of the drugs in combination as well as separately; individually each drug extended lifespan by 30%, in combination lifespan was increased by 48% compared to controls. 

"Previous studies in fruit flies have achieved lifespan extensions of about 5-20%, so we found it was quite remarkable that this drug combination enabled them to live 48% longer," Dr Castillo-Quan said.

In addition to acting on separate signalling pathways the drugs appeared to complement each other to reduce the side effects: rapamycin has an undesirable effect on fat metabolism which was cancelled by lithium when given together. 

To better understand how the drugs work together this research is ongoing, and the team hopes to move to more complex animals to gauge effects on the entire body before progressing to human trials. 

"There is a growing body of evidence that polypills -- pills that combine low doses of multiple pharmaceutical products -- could be effective as a medication to prevent age-related diseases, given the complex nature of the ageing process. This may be possible by combining the drugs we're investigating with other promising drugs, but there is a long way to go before we will be able to roll out effective treatments,:” says Principal investigator, Professor Linda Partridge (UCL Institute of Health Ageing and Max Planck Institute for Biology of Ageing).

"My research groups are working to understand the mechanism of the ageing process in order to find ways to help people stay healthy for longer. We are not trying to cheat death, but help people be healthy and disease-free in their final years," she said.