Urolithin A treatment slows reproductive decline in wild type.

(A) Reproductive span of N2 control 0.3% DMSO (n = 100) and N2 50μM UA, 0.3% DMSO (n = 100). Treatment started on Day 1 of adulthood. (B) Reproductive span of N2 hermaphrodites with Urolithin A treatment starting at Day 4 of adulthood is improved. Both control (n = 100) and experimental (n = 100) groups began 0.3% DMSO at Day 1 and UA treatment began at Day 4 in the experimental group. p = 0.0062 (C) Reproductive span of pink-1(tm1779) is unchanged with UA treatment. Control 0.3% DMSO (n = 100) and experimental 50μM UA, 0.3% DMSO (n = 100). In A and C mated hermaphrodites were loaded into Celab and started treatment on Day 1. (D) Representative images of oocyte quality in control (left panel) and UA treated (right panel) N2 worms at Day 6. Highlighted features include: embryos in the uterus (white arrows), the -1 oocyte (white asterisk), and oocyte quality decline phenotypes (yellow text). (E) Quantification of oocyte quality phenotypes at Day 6 of adulthood in control (n = 53–55) and UA treated groups (n = 48–50). (F) Representative images of oocyte quality in control (left panel) and UA treated (right panel) fzo-1(tm133) worms at Day 6. Highlighted features include: embryos in the uterus (white arrows), the -1 oocyte (black asterisk), and oocyte quality decline phenotypes (yellow text). (G) Quantification of oocyte quality phenotypes at Day 6 of adulthood in fzo-1 control (n = 38–43) and fzo-1 UA treated groups (n = 37–41). (H) Representative images of oocyte quality in control (left panel) and UA treated (right panel) drp-1(tm1108) worms at Day 6. (I) Quantification of oocyte quality phenotypes at Day 6 of adulthood in drp-1 control (n = 52) and drp-1 UA treated groups (n = 50). (J) Wild type requires both fission and fusion, but not mitophagy, to maintain a normal reproductive span. Reproductive longevity in daf-2 requires fissioned mitochondria, which are then primed for and utilize mitophagy to maintain reproductive longevity through oocyte quality maintenance. (K) Urolithin A, a mitophagy promoter, extends reproductive span in wild type with adult only treatment at Day 1 or Day 4 of adulthood. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.