Figure 2p16-3MR mice were treated with vehicle (PBS, 7 consecutive days), doxorubicin (5 mg/kg, 3 consecutive days) or abemaciclib (50 mg/kg, 7 consecutive days). n=6 mice/group. 14 dpt, bioluminescence was visualized and quantified by the IVIS spectrum in vivo imaging system, as shown by representative bioluminescence images (A) and quantification (B). Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. p16-3MR mice were treated with vehicle (PBS, 7 consecutive days), doxorubicin (5 mg/kg, 3 consecutive days) or abemaciclib (50 mg/kg, 7 consecutive days). n=6 mice/group. RNA isolated from kidneys and mRNA encoding p16 quantified by qRT-PCR (C). SA-β-gal activities in vehicle-, doxorubicin- or abemaciclib-treated mouse kidney sections at 15 dpt quantified (E). Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. Representative images (D) to visualize SA-β-gal activities in vehicle-, doxorubicin- or abemaciclib-treated mouse kidney sections at 15 dpt (arrows indicated positive area; scale bar, 1 mm; n=3 mice/group) (F) p16-3MR mice were treated with abemaciclib (50 mg/kg, 7 consecutive days) ± pifithrin-α (2 mg/kg, 7 consecutive days). Values indicate the ratio of post-treatment bioluminescence to pre-treatment (n=5 mice/group). Data information: Data are means ±SD. Unpaired student t-test. *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. (G) RNA was isolated from abemaciclib ± pifithrin-α treated kidneys and mRNA encoding p16 and p21 genes was quantified by qRT-PCR and normalized on tubulin (n=5 mice/group). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), physical performance was measured by rotarods assay at 15 dpt Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), grip strength meter at 7 dpt and 14 dpt (I) Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. dpt, days post treatment. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), hanging tests were performed at 7 dpt and 14 dpt and normalized to weights Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. dpt, days post treatment. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), (K) Relative weight changes were calculated at 7 dpt and 14 dpt. Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. dpt, days post treatment. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), Red blood cells (L) and white blood cells (M) were counted at 15 dpt. Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant. For the doxorubicin or abemaciclib treated mice (n=6 mice/group), Percentage of T cells, B cells, granulocytes and macrophages were determined by flow cytometry analysis (N). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant.