Figure 3. SIR-2.1 is required for SA-mediated lifespan extension. (A) Synthetically purified IsoKs decrease biochemical activity of rhSIRT1. Recombinant human SIRT1 was incubated with increasing concentrations of IsoK and enzymatic activity was assessed using a luminescence based assay. Concentration-response curves were generated and IC50 values were calculated from three independent experiments. (B) Kaplan-Meier survival curves depicting effects of SA administration on lifespan of non-functional SIR-2.1 mutant. (C) Summary of SA-treated SIR-2.1 mutant median lifespan. SA administration does not affect median lifespan of SIR-2.1 mutants. Data are expressed as means ± SEM from four independent experiments. P = 0.70. (D) Changes in lipofuscin autofluorescence accumulation with age. Compared to vehicle control in WT animals, SA response profiles indicate neither dose of SA were able to decrease the accumulation of lipofuscin. Data are expressed as means ± SEM from four independent experiments. P = 0.5. (E) Changes in pharyngeal pumping rate in SA-treated SIR-2.1 mutants. Administration of SA failed to preserve pharyngeal pumping rate. Data are expressed as means ± SEM from four independent experiments. P = 0.5.