Dr Manish Chamoli in the lab of Gordon Lithgow at the Buck Institute (Right)
David Weinkove, 15 June 2023
A recent research article in Science showed that supplementing with taurine slows ageing across a number of species: mouse, zebrafish, monkey and my favourite model organism the worm C. elegans. The worm may seem a lowly model organism in this company but it has the potential to help bring this breakthrough to the clinic.
I chatted with Dr Manish Chamoli, the lead scientist of the C. elegans work in this study. Manish is a Research Scientist in the lab of Gordon Lithgow at the Buck Institute in California. Manish told me that the taurine study did not start in C. elegans. In fact, it started with the observation that taurine levels dropped in many species with age and that supplementation in mice improved health. It was originally planned to use C. elegans to demonstrate that, as found in mice, that taurine supplementation improved several of the cellular hallmarks of ageing. This C. elegans work has been done by Manish but most of it was not included in the Science paper.
C. elegans instead was used to investigate the mechanism of action by which taurine affects ageing. Understanding the mechanism is essential to convince the medical community and investors to progress taurine supplementation to clinical practice. One putative mechanism is that taurine forms a specific molecule in the mitochondria (a tRNA) and thereby promotes the expression of a protein required for mitochondrial function – complex I of the electron transport chain. The data in the study from C. elegans was consistent with taurine being required for this function. However it is not yet known if this mitochondrial function is the mechanism by which taurine supplementation slows ageing. With its powerful genetic tools and fast readout for ageing, using lifespan, (or even faster using Magnitude Biosciences’ WormGazerTM technology), C. elegans is the best model system to work out the molecular mechanism.
Manish and Gordon are working on this problem right now. Once they have identified the mechanism it would need to be validated in mammalian systems and in humans, and then would lead to much greater understanding of taurine supplementation. Clinicians would have molecular markers to understand what taurine levels constitute a clinical deficiency for ageing, how much supplementation is needed to rescue that deficiency and how to treat patients accordingly.
Manish is excited about this possibility and is enthusiastic about what C. elegans can do for therapeutics in this area. Like me, he wants the worm to be a standard part of the drug discovery toolkit!