Spotlight on a Pump Priming Award Winner: Mechanisms of Taurine regulation

May 9, 2024

As an inaugural blog post for the UKAN site, we are delighted to shine the spotlight on a recent Pump Priming Award winning team and their work…

Mechanisms of Taurine regulation
Lola Morrin, Dan J. Hayman and Mirre J. P. Simons, University of Sheffield

Meet the team: Lola is an undergraduate student based at Sheffield Hallam University, currently undertaking a placement year in the Simons Lab. Dan is a postdoc in the Simons Lab at the University of Sheffield, interested primarily in identifying treatments that can improve healthy lifespan, using fruit flies to identify fundamental ageing mechanisms that are translatable across biology.

The Project: Dietary interventions require precision to work and be implemented. Interactions with existing morbidities and heterogeneity between individuals in lifestyle and physiology are expected. Mechanistic understanding of these interventions can ultimately aid translation by optimising benefits and reducing possible side-effects. Work presented at the Nutritional Resilience for Healthy Ageing conference (Belfast, 2023) highlighted that results are not always as expected, with limited success in protein supplementation studies in the elderly and surprising differences in animal versus plant sources of protein. We know there are interactions between amino-acid sensing and overall metabolism. In its most extreme form single amino-acids added to a sucrose only diet result in whole animal depletion of fat resources. Perhaps fitting with this observation, recent work suggests a single amino-acid, Taurine, a key ingredient in many popular energy drinks, declines with age and when supplemented increases lifespan in C. elegans and mice (Singh et al., 2023). Understanding the mechanisms of how Taurine affects physiology will be key to translate this more precise nutritional intervention to the elderly.

Under highly controlled conditions, we tested whether Taurine affected development using fruit flies, a commonly used and highly efficient model organism. We found that increasing dietary Taurine reduced the ability of flies to successfully develop (Figure A). We then confirmed this effect across 18 inbred genetic lines, but also found strong genetic variation (Figure B). In previous work, far higher concentrations of Taurine (up to and including 25.0 g/L) have been found to have no effect on lifespan in adult flies (Massie et al., 1989). In contrast to the literature, all concentrations we tested (including 25.0 g/L) were highly toxic to flies and they died within a matter of days (Figure C), noting here that the lifespan of a fly is well over 60 days on the control diet (data not shown).

Our next steps are to seek additional funds to utilise the genetic variance of response to Taurine identified in Figure B to identify mechanisms behind this effect, through a genome-wide association study, and to then subsequently test mechanisms directly using the functional genetic tools readily available in the fly. Our work will include the established sequenced fly lines of the Drosophila Genetic Reference Panel, and lines we generated and sequenced ourselves. This will enable us to pinpoint genes and key pathways related to Taurine toxicity and regulation. We are also currently testing lower Taurine doses to identify the critical dose at which this micronutrient begins to exert the observed detrimental effect on survival, thus pinpointing precisely how much Taurine is too much.

References
Massie, H.R., Williams, T.R. and DeWolfe, L.K., 1989. Changes in taurine in aging fruit flies and mice. Experimental gerontology, 24(1), pp.57-65.
Singh, P., Gollapalli, K., Mangiola, S., Schranner, D., Yusuf, M.A., Chamoli, M., Shi, S.L., Lopes Bastos, B., Nair, T., Riermeier, A. and Vayndorf, E.M., 2023. Taurine deficiency as a driver of aging. Science, 380(6649), p.eabn9257.