Extended Data Fig. 8: Aldometanib improves lifespan and healthspan in C. elegans.

a, aldometanib activates AMPK in C. elegans via the lysosomal pathway. N2, aak-2 (left), lmtr-2 (middle), and axl-1 (right) nematodes were cultured on the agar plates containing aldometanib at 10 μM, followed by determining levels of p-AMPKα by immunoblotting. b, aldometanib inhibits TORC1 in C. elegans. The N2 nematodes (HLH-30::GFP) expressing GFP-tagged HLH-30, nematode orthologue of TFEB, were cultured on the agar plates containing 10 μM aldometanib for 1 day, followed by determining the localisation of HLH-30 by fluorescent staining. Representative images are shown. c, d, aldometanib promotes pharyngeal pumping rates and brood size of C. elegans. N2 and aak-2 nematodes were cultured on the agar plates containing aldometanib at 10 μM and 12.5 μM. Pharyngeal pumping rates (c) are mean ± s.e.m., n = 9 (N2 + 12.5 μM) or 10 (others) biological replicates. Brood size (d) are mean ± s.e.m., n = 23 (N2), 11 (aak-2, control) or 13 (aak-2, aldometanib-treated) biological replicates. P values are calculated by two-way ANOVA, followed by Tukey. e, aldometanib promotes mitochondrial OXPHOS gene expression in C. elegans. N2 and aak-2 nematodes were cultured on the agar plates containing aldometanib at 10 μM for a day, followed by determining the levels of OXPHOS genes by RT-PCR. Data are shown as mean ± s.e.m., n = 3 biological replicates for each genotype/treatment, and P value by two-way ANOVA, followed by Tukey. f, aldometanib does not trigger UPR^mt in C. elegans. The hsp-6_p::gfp nematodes were cultured on the agar plates containing aldometanib at 10 μM for a day, followed by determining the fluorescent intensities of GFP. Representative images are shown on the left panel, and statistical analysis data on the right panel (left panel; shown as mean ± s.e.m., n = 30 worms for each treatment, and P value by two-sided Student’s t-test with Welch’s correction). Experiments in this figure were performed three times.

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