TY - JOUR TI - The metabolome of Mexican cavefish shows a convergent signature highlighting sugar, antioxidant, and Ageing-Related metabolites AU - Medley, J Kyle AU - Persons, Jenna AU - Biswas, Tathagata AU - Olsen, Luke AU - Peuß, Robert AU - Krishnan, Jaya AU - Xiong, Shaolei AU - Rohner, Nicolas A2 - Valenzano, Dario Riccardo A2 - Isales, Carlos A2 - Valenzano, Dario Riccardo VL - 11 PY - 2022 DA - 2022/06/15 SP - e74539 C1 - eLife 2022;11:e74539 DO - 10.7554/eLife.74539 UR - https://doi.org/10.7554/eLife.74539 AB - Insights from organisms, which have evolved natural strategies for promoting survivability under extreme environmental pressures, may help guide future research into novel approaches for enhancing human longevity. The cave-adapted Mexican tetra, Astyanax mexicanus, has attracted interest as a model system for metabolic resilience, a term we use to denote the property of maintaining health and longevity under conditions that would be highly deleterious in other organisms (Figure 1). Cave-dwelling populations of Mexican tetra exhibit elevated blood glucose, insulin resistance and hypertrophic visceral adipocytes compared to surface-dwelling counterparts. However, cavefish appear to avoid pathologies typically associated with these conditions, such as accumulation of advanced-glycation-end-products (AGEs) and chronic tissue inflammation. The metabolic strategies underlying the resilience properties of A. mexicanus cavefish, and how they relate to environmental challenges of the cave environment, are poorly understood. Here, we provide an untargeted metabolomics study of long- and short-term fasting in two A. mexicanus cave populations and one surface population. We find that, although the metabolome of cavefish bears many similarities with pathological conditions such as metabolic syndrome, cavefish also exhibit features not commonly associated with a pathological condition, and in some cases considered indicative of an overall robust metabolic condition. These include a reduction in cholesteryl esters and intermediates of protein glycation, and an increase in antioxidants and metabolites associated with hypoxia and longevity. This work suggests that certain metabolic features associated with human pathologies are either not intrinsically harmful, or can be counteracted by reciprocal adaptations. We provide a transparent pipeline for reproducing our analysis and a Shiny app for other researchers to explore and visualize our dataset. KW - Astyanax mexicanus KW - cavefish KW - metabolomics KW - resilience KW - ageing KW - non-traditional model JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -