Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor

Regenerative capacity declines throughout evolution and with age. In this study, we asked whether metabolic programs underlying regenerative capability might be conserved across species, and if so, whether such metabolic drivers might be harnessed to promote tissue repair. To this end, we conducted metabolomic analyses in two vertebrate organism regeneration models: the axolotl limb blasmata and antler stem cells. To further reveal why some individuals have higher regenerative capacity than the elderly, we also constructed metabolic profiles for primate juvenile and aged tissues, as well as young and aged amoeba stem cells. In joint analyses, we uncovered that active pyrimidine metabolism and fatty acid metabolism correlated with higher regenerative capacity. Furthermore, we identified a potent regeneration-related metabolite for stem cell responses. One such metabolite is uridine, a pyrimidine that plays important roles in multiple cellular processes. Our findings provide a foundation for future investigations into metabolic regulation in tissue repair and regeneration.