Research Paper Volume 12, Issue 12 pp 11337—11348

Senolytic treatment strategy. (A) Scheme of the senolytic treatments strategy: C57BL/6HsdOla male mice of 12 weeks of age were fed on 45% HFD for 4 months. Then, 5 cycles of senolytic treatment and glucose homeostasis assessment were undertaken: first, mice were treated daily by oral gavage with the senolytic or its vehicle for 5 consecutive days, and rested for 1 week. The third week of each cycle, an insulin tolerance test (I) and a glucose tolerance test (G) were performed. After the fifth cycle was finished, mice were treated again with senolytics for 5 consecutive days by oral gavage, and sacrificed at the fifth day of treatment (Sac). (B) Mouse body weight at the first day of every senolytic treatment, indicated for each of the 5 cycles. (C) Food intake recorded at cycles 1 and 2. (D) Blood samples were collected every fifth day of each cycle of senolytic treatments, right after the last oral administration, and platelet counts were determined. V-Nav: vehicle for navitoclax. Nav: navitoclax. V-D/Q: vehicle for dasatinib/quercetin. D/Q: dasatinib/quercetin. Bars and dots represent the average of the indicated number of mice. Error bars represent the standard error of the mean (s.e.m.). Statistical significance was assessed using the two-way ANOVA test with Sidak’s correction for multiple comparisons (B); the one-way ANOVA test with Tukey’s correction for multiple comparisons (C); or the unpaired two-tailed Student's t-test (D). **, p<0.01; ***, p<0.001.