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Experimental Drug Cocktail Yields Greatest Lifespan Extension Ever Seen in Animals

PETER DOCKRILL
23 OCT 2018

Pioneering research into anti-ageing mechanisms in animals has almost doubled the lifespan of the test subjects used in the experiments.

A team of scientists in Singapore tried experimental combinations of different compounds on the roundworm Caenorhabditis elegans, and found that cocktails made up of already existing drugs could both slow the effects of ageing and significantly boost the animals' longevity.

 

"We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved ageing pathways and mechanisms using drug combinations," write authors from the National University of Singapore (NUS) and Yale-NUS College.

While nematode worms are obviously an extremely different lifeform to human beings, C. elegans is often used as a proxy in examinations of ageing and related processes because their short lifespans make them easy for scientists to monitor.

And while it might not look like it on the surface, they also share enough similarity with human genetics to provide an important model for us to learn how various chemical interactions inside the body play out.

234 drug cocktail 1Microcscope image of the C. elegans worms used in the study (Jan Gruber)

In this case, the researchers wanted to see how drugs that are already known to boost longevity in animals – like the chemical rapamycin – might have their effects boosted when paired with complementary compounds.

For example, rapamycin – aka sirolimus, which helps the body accept organ transplant – has been shown to boost the lifespan of fruit flies and mice in addition to nematodes.

 

But hypothetically, when rapamycin is combined with other chemicals that target different chemical pathways, the resulting cocktail might effectively slow down numerous chemical processes related to ageing at the same time.

"The central idea of our approach is that targeting different sub-sets of the gene regulatory network controlling ageing will recruit genes and mechanisms that are not affected by either drug alone," the authors write in their paper.

In a number of experiments with rapamycin and also the compounds rifampicin, psora–4, metformin, and allantoin, the team found that a cocktail of two drugs paired boosted lifespan in the worms more effectively than when the drugs were used in isolation.

Even better, a combination involving three of the compounds almost doubled nematode longevity – a result the researchers say is the greatest lifespan extension ever reported for a drug intervention in adult animals.

While we're a long way off trialling these kinds of experimental cocktails in human tests, the researchers say the "synergistic benefits" of drug combinations in worms can extend animal lifespan while boosting the amount of time the subject enjoys optimal health, and without reducing fertility.

 

Preliminary tests suggest the drug combinations were not harmful, and separate experiments with the fruit fly Drosophila melanogaster reveal that some of the synergistic combinations were conserved across species – which bodes well for efforts to use some of what we've learned here, one day, in people.

"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," explains principal investigator of the study, biochemist Jan Gruber from Yale-NUS College.

"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."

The findings are reported in Developmental Cell.