26th October 2018
New drug combination doubles lifespan of worms
The life-extending effects of a new drug combination, observed in the worm Caenorhabditis elegans (C. elegans), are among the greatest yet seen for any study of adult animals. These findings could one day translate into treatments that delay aging in humans.
A team of researchers led by Dr Jan Gruber from Yale-NUS College has discovered a combination of pharmaceutical drugs, which not only increases the healthy lifespan of microscopic worms (C. elegans), but also delays the rate of aging in them. The breakthrough, published this month in the peer-reviewed journal Developmental Cell, lays crucial groundwork for designing drug combinations that produce the same effect in mammals.
"Many countries are facing problems related to aging populations," explains Dr Gruber. "If we can find a way to extend healthy lifespan and delay aging in people, we can counteract the detrimental effects of an aging population – providing countries not only medical and economic benefits, but also a better quality of life for their people."
The study was carried out by Dr Gruber and his team in collaboration with researchers from the Singapore Lipidomics Incubator (SLING) at the Life Sciences Institute of NUS. The scientists wanted to know to what extent healthy lifespan could be extended by combining drugs targeting several pathways (underlying biological mechanisms) known to affect lifespan. For instance, the drug rapamycin is currently administered following organ transplants to prevent the body's immune system from rejecting transplanted organs, but previous experiments have shown that it has life-extending effects in a number of organisms including the C. elegans worms, fruit flies and mice.
Dr Gruber's team administered combinations of two or three compounds targeting different aging pathways to C. elegans. The 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 was among the largest ever reported for any drug treatment in adult animals.
The drugs had no adverse effect on the worms' health. The researchers also discovered that across all ages, the treated worms were healthier and spent a larger percentage of their already extended lifespans in good health. This is an important point for any potential future treatments in humans, as increased health span – not just increased lifespan – would have significant medical and economic benefits.
"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," Dr Gruber explains. "These diseases currently require very expensive treatments – so the economic benefits of being healthier for longer would be enormous."
He cited a 2017 study, which determined that if US citizens' aging rate was decreased by 20%, the US government would save $7.1 trillion in public health costs over the next 50 years.
Dr Gruber's lab also collaborated with Yale-NUS Associate Professor of Life Science, 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 would suggest that the biological mechanisms regulating these drug interactions on aging are ancient. This makes it more likely that similar interactions between aging pathways could be targeted in humans.
According to Dr Gruber, this study is a proof-of-principle, showing that pharmacological intervention targeting multiple aging pathways is a promising strategy to slow aging and dramatically extend healthy lifespan in adult animals.
The next steps for this research are as follows. The first will be to extend this approach with the aim of designing interventions even more effective than the ones developed in this study. The second will involve determining the precise molecular and biological mechanisms of how the drugs interact to delay aging and increase lifespan, in order to develop computer models to simulate these interactions, allowing researchers to test thousands more combinations. The ultimate goal of this line of research would be to develop drug interventions safe enough to slow aging in humans, a goal that is also pursued by many other research teams around the world.
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