Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages.

Whether a decline in taurine drives aging is debated, and despite high millimolar intracellular concentrations, its function as a potential guardian of cytosolic homeostasis is unclear. Here, we show that aging increases circulating taurine concentrations in humans and mice. Further elevating taurine in aged mice enhances health span, engaging anti-inflammatory pathways previously linked to youthfulness, and reduces mortality from sepsis and inflammasome-mediated inflammation, suggesting an enantiostatic response. Mechanistically, diverse NLRP3-specific "danger signals" induce taurine efflux from macrophages as a proximal step to activate the inflammasome and the resultant pyroptosis. Taurine restoration in macrophages prevents NLRP3-induced trans-Golgi network disassembly, thereby suppressing NLRP3 inflammasome activation. Conversely, lowering taurine biosynthesis combined with reduced bioavailability in macrophages exacerbated inflammasome activation. In humans, sustained caloric restriction elevates adipose tissue taurine and is accompanied by lower inflammation. Together, we identify taurine as an immunometabolic rheostat that links danger sensing to NLRP3 inflammasome activation, suggesting taurine-based strategies to alleviate inflammaging and inflammasomopathies.