Figure 5. Mianserin attenuates drift-variance in peripheral tissues via SER-5.
(a) Bar graphs quantifying transcriptional drift (log fold-changes in gene expression) as measured by qRT-PCR in 5-day-old N2 and ser-5(ok3087) animals treated with mianserin, relative to water-treated N2. Mianserin treatment increases expression of genes drifting down with age and decreases expression of genes drifting up with age in N2, but not in ser-5(ok3087) mutants. (See 5b). *P<0.05, **P<0.01, ***P<0.001,t-test; Error bars: S.E.M. (b) Log fold-change in gene expression as a function of age for stress response genes shown in a. Blue arrows indicate how mianserin treatment corrects age-associated changes in gene expression toward an expression pattern as seen in young adults. (c) Bar graphs quantifying log fold-changes in gene expression in 1-day-old N2 and ser-5(ok3087) animals treated with paraquat, relative to water-treated N2 animals. N2 and ser-5(ok3087) show an identical response to paraquat. (d) Mianserin treatment on day 1 of adulthood enhances transcription of sod and hsp-16.x genes in response to an 8h paraquat treatment on day 5 in wt (N2) animals compared to water treated controls. In contrast, mianserin treatment of ser-5(ok3087) animals did not enhance transcription of sod and hsp-16.x genes. mRNA levels of genes were evaluated by qRT-PCR and plotted as fold induction (PQ/water) (Y-axis) for each gene. (e) Survival plot of mianserin-treated and untreated N2 and ser-5(ok3087) animals. ***P<0.001, *P<0.05, Mantel–Haenszel version of the log-rank test. f) Percent increase in lifespan as a function of mianserin concentration. Mutations in ser-5 or synaptic components rendered the animals partially or completely resistant to mianserin-induced lifespan extension. See Figure 5—figure supplement 1 for additional data, and Table 8 for detailed statistics.
Figure 5—figure supplement 1. This figure relates to Figure 5e in main text.
