Fig. 2: 3HAA mediates lifespan extension from reduced haao-1 activity.

a C. elegans lacking haao-1 (haao-1(tm4637)) accumulate a red coloration with age relative to wild type. Animals shown are age 21 days from egg. Cutout provides an enlarged view of the head region. Arrows highlight areas of distinct coloration difference between wild type and haao-1 animals. b NGM plates supplemented with 3HAA are red in color. c 3HAA levels measured by LC-MS/MS are elevated ~10-fold in 8-day-old worms subjected to haao-1(RNAi), but not kynu-1(RNAi) or tdo-2(RNAi), relative to EV(RNAi) (N = 9 biologically independent samples per condition). d Supplementing C. elegans media with 0.01 to 1 mM 3HAA extends lifespan. e 1 mM 3HAA mimics lifespan extension from haao-1 knockdown or deletion and similarly f does not affect brood size and g elevates thrashing capacity in liquid across lifespan. For box-and-whisker plots, center line represents median, boxes indicate first and third quartiles, and whiskers represent 5th and 95th percentiles. h 1 mM 3HAA increases lifespan in animals subjected to tdo-2(RNAi), kynu-1(tm4924) single deletion, or kynu-1(tm4924) haao-1(tm4637) double deletion to a degree similar to wild type animals; lifespan extension is largely eliminated in haao-1(tm4637) animals. Colored text indicates change in mean lifespan relative to control. Error bars indicate standard error of mean. *p < 0.05, **p < 0.01, ***p < 0.001 (two-sided Welch’s t test, panels c, f, g; log rank test, panels d, e, h). Summary statistics are provided in Supplementary Data 1 and source data are provided in Source Data.