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. 2020 Dec 1;9:e62048. doi: 10.7554/eLife.62048

Figure 1. ISRIB resets the ISR in the brain of old mice.

(A) Experimental dosing scheme: ISRIB treatment denoted by syringes (three injections). (B) ISRIB treatment reduced ATF4 protein levels chronically 18 days after ISRIB treatment was complete. One-way ANOVA (F = 18.8, p<0.001); with Tukey post-hoc analysis. (C) Modest age-induced increases in p-GCN2 when comparing young and old male mice. One-way ANOVA (F = 6.6, p<0.05); with Tukey post-hoc analysis. (D, E) Age and ISRIB administration did not impact p-PERK or p-PKR protein levels. Brain lysates of specific protein levels listed normalized to actin. Young n = 5, Old = 3, Old + ISRIB = 3. Individual animal values represented by dots; lines depict group mean ± SEM. *p<0.05; ***p<0.001.

Figure 1.

Figure 1—figure supplement 1. ISRIB downregulates ATF4 during administration.

Figure 1—figure supplement 1.

The impact of ISRIB on known ISR activation pathways was investigated by western blot analysis of brain lysates after 3 ISRIB injections. (A) Raw western blot data. Each lane represents an individual animal brain extract. (B) ISRIB treatment reduced ATF4 protein levels during drug administration. Old males (Chou et al., 2018) and females (Anderson et al., 1998): Old n = 10; Old + ISRIB n = 10. Student’s t-test. *p<0.05. Individual animal values represented by dots; lines depict group mean ± SEM.
Figure 1—figure supplement 2. ISRIB down-regulates the ISR in the brain of old mice.

Figure 1—figure supplement 2.

The impact of ISRIB on known ISR kinases and activation pathways was investigated by western blot analysis of brain lysates (raw western blot data) at day 20. (A) ATF4 (B) p-GCN2, p-PKR, p-PERK. Each lane represents an individual animal brain extract.