Three-drug combo greatly extends fruit fly lifespan
The complex interplay of various processes and mechanisms that contribute to aging means it’s unlikely we’ll discover a single “magic bullet” to prevent age-related diseases. But new research led by University College London and the Max Planck Institute for Biology and Ageing is potentially as close as anything we’ve seen. The scientists have been able to extend the lifespan of fruit flies by 48 percent using a triple drug combination made up of drugs already used in people.
"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," says study co-lead author, Dr Jorge Castillo-Quan. "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 aging process."
The three drugs making up the combo include lithium, which is used as a mood stabilizer, trametinib, a cancer drug that inhibits MEK1 and MEK2 enzymes, and rapamycin, an immune system regulator produced by bacteria that was first found in a soil sample from Easter Island and has been found to improve learning and memory in mice.
Individually, all three drugs had been shown to increase the lifespan of fruit flies (Drosophilia) in previous studies, and the researchers saw similar results in this new study with each drug extending the lifespan of the fruit flies by an average of 11 percent. But the extension increased around 30 percent when two of the drugs were combined, and reached 48 percent when all three drugs were used.
Rather than just providing their own lifespan-extension capabilities, the drug combination appears to be greater than the sum of its parts, with the individual drugs complementing each other to reduce side effects of the others. As an example, the researchers point out that, when taken on its own, rapamycin can have an effect on fat metabolism similar to insulin resistance in people, but they say the lithium appeared to cancel out this negative side effect.
However, the cumulative anti-aging effects of the drug cocktail are primarily due to the drugs acting on separate signaling pathways in the nutrient sensing network. This network adjusts the body's response to changes in nutrient levels and, importantly, isn't just found in fruit flies, but appears in everything from worms to humans.
With the ultimate goal of testing the drug combination in people, the researchers will first seek to better understand how the drugs work together and gauge their effects on the entire body. They then hope to conduct experiments involving more complex animals, such as mice, before moving onto 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 aging process," says principal investigator, Linda Partridge. "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. My research groups are working to understand the mechanism of the aging 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."
This isn't the first time researchers have managed to lengthen the lifespan of an organism using a novel drug cocktail. Last year, a team extended the lifespan of a microscopic worm called Caenorhabditis elegans (C. elegans). Interestingly, rapamycin was one of the three drugs included in that three-drug combo.
The latest study was published in Proceedings of the National Academy of Sciences (PNAS).
Source: University College London