(A) Worm motility decline is enhanced in unc-104 lof mutant, but mitigated in UNC-104 overexpression backgrounds. Total number analyzed: day 1: 15 (wildtype), 9 (unc-104(wy711)), 7 (unc-104(e1265/+), 7 (Prab-3::unc-104); day 12: 36 (wildtype), 20 (unc-104(wy711)), 23 (unc-104(e1265/+), 28 (Prab-3::unc-104); day 18: 25 (wildtype), 15 (unc-104(wy711)), 17 (unc-104(e1265/+), 21 (Prab-3::unc-104); (B) UNC-104 improves the motility defect at advanced ages (d21), and has similar protective functions when expressed in motor neurons (Punc-17 + Punc-47). Total animals analyzed: day 18: 25 (wildtype), 16 (Prab-3::unc-104 line #1), 16 (Prab-3::unc-104 line #2), 13 (Motor neuron::unc-104);*, P<0.05; **, P<0.01; ***, P<0.001. One-way ANOVA. (C) UNC-104 over-expressing animals are more active at d21. Upper panel, representative images of the locomotion traces left on the bacterial lawns in three hours. Lower panel, locomotion trajectories. The asterisks mark the starting points where animals are placed on the plates. (D) Quantification of the total distance the worms moved in three hours. Total animals analyzed: 13(wildtype), 15 (Prab-3::unc-104 line #2). ***, P<0.001. Unpaired student t test. The error bars stand for 95% confidence intervals (CI).