Senolytics increase urinary and kidney α-Klotho in old or obese mice. (a) Naturally-aged male mice (28-29-month-old, n = 10 in each group) were treated with vehicle, Dasatinib plus Quercetin (D+Q), or Fisetin. Urinary α-Klotho was measured by ELISA and expressed as a function of creatinine. One-way ANOVA: F = 6.39; p < 0.05, R2 = 0.30; *p = 0.02, **p < 0.01. (b) DIO mice (male, 10-month-old, n = 8) were treated with vehicle or D+Q and urinary α-Klotho was assayed by ELISA and expressed as a function of creatinine. Unpaired T test; **p < 0.01. (c) Six-month-old male mice (n = 6 in each group) were transplanted i.p. with senescent preadipocytes. After 3 months, they were treated with vehicle, D+Q, or Fisetin. Urinary α-Klotho was assayed by ELISA and expressed as a function of creatinine. One-way ANOVA and post hoc Tukey's tests: Kruskal-Wallis statistic=10.19; *p = 0.02, **p < 0.01. (d) Kidney α-Klotho protein was also assayed in the same transplanted mice by Western blotting. One-way ANOVA: F = 24.24; p < 0.001, R2 = 0.83; ***p < 0.001.