The study, published in the journal Developmental Cell, lays crucial groundwork for further research into designing drug combinations that produce the same effect in mammals.
“Many countries in the world, including Singapore, are facing problems related to ageing populations,” said Jan Gruber from Yale-NUS College in Singapore. “If we can find a way to extend healthy lifespan and delay ageing in people, we can counteract the detrimental effects of an ageing population, providing countries not only medical and economic benefits, but also a better quality of life for their people,” Gruber said.
The team wanted to find out to what extent healthy lifespan could be extended by combining drugs targeting several pathways known to affect lifespan. For instance, the drug rapamycin is currently administered following organ transplants to prevent the body’s immune system from rejecting the transplanted organs. However, previous experiments showed that it extends the lifespan of many organisms, including the Caenorhabditis elegans (C elegans) worms, fruit flies and mice.
The researchers administered combinations of two or three compounds targeting different ageing pathways to C elegans. Results showed that two drug pairs in particular extended the mean lifespan of the worms more than each of the drugs individually, and in combination with a third compound almost doubled mean lifespans. This effect is larger than any lifespan extension that has previously been reported for any drug intervention in adult animals, researchers said. The drug treatments had no adverse effect on the worm’s health.
The researchers also discovered that across all ages, the treated worms were healthier and spend a larger percentage of their already extended lifespans in good health. This is an important point for potential future human ageing interventions as increased health span, not just increased lifespan, would have significant medical and economic benefits, researchers said. “We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer’s disease,” Gruber said.
“These diseases currently require very expensive treatments, so the economic benefits of being healthier for longer would be enormous,” he said.
Gruber’s lab also collaborated with Yale-NUS Associate Professor Nicholas Tolwinski, and found that a species of fruit flies (Drosophila melanogaster) treated with a similar drug cocktail also experienced significant lifespan extension. That two such evolutionarily-distinct organisms experience similar lifespan extensions suggests that the biological mechanisms that regulate these drug interactions on ageing are ancient, making it more likely that similar interactions between ageing pathways could be targeted in humans, researchers said.
According to Gruber, this study is a proof-of-principle, showing that pharmacological intervention targeting multiple ageing pathways is a promising strategy to slow ageing and dramatically extend healthy lifespan in adult animals.