Fig. 3: PZ effectively clears SCs without causing thrombocytopenia in naturally aged mice. | Nature Communications

Fig. 3: PZ effectively clears SCs without causing thrombocytopenia in naturally aged mice.

From: Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity

Fig. 3: PZ effectively clears SCs without causing thrombocytopenia in naturally aged mice.

a Mice received an IP injection of vehicle (VEH), ABT263 (ABT) or PZ, and platelets (PLTs) were numerated at 6 h, day 1, 3, 5, 7, and 10 after the injection. Data are represented as mean ± SEM (n = 3 mice/group). a p < 0.05 vs. control, determined by one-way ANOVA with Tukey’s post-hoc tests. b Illustration of the experiment design. Naturally aged mice (Aged) were given 41 μmol/kg of PZ or ABT263 by IP injection every 3 days (q3d) for a total of 7 injections and euthanized 6 days after the last treatment to harvest various tissues and cells for analyses. Control untreated young mice (Young) mice were analyzed as aged mice without any treatment. Blood PLTs counts in Young and naturally aged mice were measured 1 day after receiving the 1st (c) and 7th (d) IP injection of VEH, ABT263 (ABT) or PZ. The data presented are mean ± SEM. a, b, c p < 0.05 vs. Young, Aged + VEH and Aged + ABT, respectively. Expression of Cdkn2a (e), Cdkn1a (f), Il6 (g), Cxcl12 (h), Mmp3 (i), and Tnfsf11 (j) mRNA in the spleen, and expression of Cdkn2a mRNA in the liver (k), lung (l), kidney (m), and fat (n) of Young and naturally aged mice treated with VEH, ABT or PZ measured by quantitative PCR (qPCR) as illustrated in (b). The data presented are mean ± SEM. a, b, c p < 0.05 vs. Young, Aged + VEH and Aged + ABT, respectively. Data in c–n were analyzed by one-way ANOVA with Tukey’s post-hoc tests, or Kruskal–Wallis one-way ANOVA with Dunn’s post-hoc test, with n = 8, 8, 6, and 7 mice per group for Young, VEH-, ABT263-, and PZ-treated naturally aged mice, respectively. n n = 7, 7, 6, and 7 mice per group for Young, VEH-, ABT263-, and PZ-treated naturally aged mice, respectively. Source data are provided as a Source Data file. The exact P values are provided in the Source Data file.

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