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The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

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Ethosuximide treatment extended lifespan and stimulated egg laying in cca-1 null-mutants.

(A) Ethosuximide extended the lifespan of cca-1(gk30) mutants. Wild-type or cca-1(gk30) hermaphrodites were cultured with 0 mg/ml or 4 mg/ml ethosuximide (+ETH 4) from conception until death. The mean lifespans in days±SD for WT, WT+ETH 4, cca-1, and cca-1+ETH 4 were 16.1±3.3 (n = 110), 19.5±4.8 (n = 120), 15.2±4.9 (n = 140), and 20.8±6.6 (n = 110), respectively. The differences in mean lifespan of WT compared to WT+ETH 4 and cca-1 compared to cca-1+ETH 4 were statistically significant, p<0.0001 (Student T-test). (B) cca-1 mutants responded to ethosuximide stimulated egg-laying. The mean number of eggs laid±SD by wild-type animals (blue circles) was 0.0±0.0, 0.7±2.2, 2.0±2.5, and 6.8±5.2 for ethosuximide concentrations of 0, 4, 8, and 12 mg/ml, respectively. The mean number of eggs laid±SD by cca-1(ad1650) mutant animals (red squares) was 0.0±0.0, 0.25±1.0, 2.7±3.1 and 8.0±5.6 for ethosuximide concentrations of 0, 4, 8, and 12 mg/ml, respectively. n>23 for all trials. Differences in egg-laying between WT and cca-1 at ethosuximide concentrations of 0, 4, 8 and 12 mg/ml were not statistically significant, p>0.05 (Student T-test).

Figure 1

doi: https://doi.org/10.1371/journal.pgen.1000230.g001