Better together? Testing the first combination therapies for longevity

The normal mode of drug discovery is a pretty singular affair: one compound, one disease. This is enough for many traditional diseases, but when you’re facing a complex phenomenon built on innumerable pathways like aging, where existing treatments only scratch the surface, you need to get a little more creative.

complex phenomenon built on innumerable pathways

Researchers studying genetic modulators of lifespan have already have, for instance by mimicking the pro-longevity effect of caloric restriction in worms via a combination of mutations in CR-affected pathways. If that could be bottled and sold to humans, it would be the most effective existing longevity pharmaceutical by a mile–but so far, virtually no attempts have been made to replicate the effect in pill form.

a combination of mutations in CR-affected pathways

That is, until researchers at the National University of Singapore struck out into uncharted territory recently (preprint here), hoping genetic interventions weren’t the only ones that could play well with others. They examined 10 compounds, chosen for their evolutionarily conserved mechanisms through pathways like AMPK and TOR, and were able to reproduce the effects of five: the familiar TOR inhibitor rapamycin, the anti-diabetic agent metformin (of TAME fame) and three relative unknowns–rifampicin, psora-4 and allantoin.

(preprint here)rapamycinmetforminTAME



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