biostudies-literatureKim JNational Research Foundation of Korea6554https://www.ebi.ac.uk/biostudies/studies/S-EPMC9628521biostudies-literatureUnknown13(1)The pathways that impact longevity in the wake of dietary restriction (DR) remain still ill-defined. Most studies have focused on nutrient limitation and perturbations of energy metabolism. We showed that the L-threonine was elevated in Caenorhabditis elegans under DR, and that L-threonine supplementation increased its healthspan. Using metabolic and transcriptomic profiling in worms that were fed with RNAi to induce loss of key candidate mediators. L-threonine supplementation and loss-of-threonine dehydrogenaseincreased the healthspan by attenuating ferroptosis in a ferritin-dependent manner. Transcriptomic analysis showed that FTN-1 encoding ferritin was elevated, implying FTN-1 is an essential mediator of longevity promotion. Organismal ferritin levels were positively correlated with chNature communicationsL-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans.PMC96285212020R1A2C2010964Kim JJo YRyu DCho DfalseL-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans.The pathways that impact longevity in the wake of dietary restriction (DR) remain still ill-defined. Most studies have focused on nutrient limitation and perturbations of energy metabolism. We showed that the L-threonine was elevated in Caenorhabditis elegans under DR, and that L-threonine supplementation increased its healthspan. Using metabolic and transcriptomic profiling in worms that were fed with RNAi to induce loss of key candidate mediators. L-threonine supplementation and loss-of-threonine dehydrogenaseincreased the healthspan by attenuating ferroptosis in a ferritin-dependent manner. Transcriptomic analysis showed that FTN-1 encoding ferritin was elevated, implying FTN-1 is an essential mediator of longevity promotion. Organismal ferritin levels were positively correlated with ch2022-01-01T00:00:00Z2022 Nov2026-05-10T06:07:53.616Z2024-12-04T01:39:55.661ZS-EPMC96285213632368310.1038/s41467-022-34265-x