Extended Data Fig. 4: Effects of normalization of glucose metabolism on senescent cells in visceral adipose tissue.

a, Protocol of the experiments to test the senolytic effects of 4 weeks of treatment with insulin. NC, normal chow; HFD, high-fat diet. b, Body weight, gonadal white adipose tissue (gWAT) weight, and fasting blood glucose of mice fed NC or HFD with or without insulin (Ins) (n = 5 each). c, Glucose tolerance test and insulin tolerance test in mice as prepared in Extended Data Fig. 4b (n = 5 each). d, SA-β-gal activity in gWAT of mice as prepared in Extended Data Fig. 4b (n = 5 each). e, Protocol of the experiments to test the senolytic effects of returning to NC after receiving HFD. NC, normal chow; HFD, high-fat diet. f, Body weight, gWAT weight, and fasting blood glucose of mice prepared according to the protocol shown in Extended Data Fig. 4e (n = 9 each). g, SA-β-gal activity in gWAT of mice as prepared in Extended Data Fig. 4f (n = 9 each). Data were analyzed by two-tailed unpaired Student’s t-test (b–d) or two-way ANOVA followed by Tukey’s multiple comparison test (for equal variance) or Dunnett’s multiple comparison test (for unequal variance) (f, g) or repeated measures analysis (c). *P < 0.05, **P < 0.01. Exact P-value: HFD versus HFD+Ins: 0.0005 (Fasting blood glucose) (b); HFD versus HFD+Ins: < 0.0001 (GTT-trend), 0.0029 (GTT-AUC), 0.0009 (ITT-trend) and 0.0058 (ITT-AUC) (c); NC versus HFD: < 0.0001 (Body weight and gWAT weight) and 0.0002 (Fasting blood glucose), NC versus HFD- > NC: <0.0001 (Body weight and gWAT weight), HFD versus HFD- > NC: 0.0073 (Body weight) and < 0.0001 (Fasting blood glucose) (f); NC versus HFD: 0.0001, and NC versus HFD- > NC: 0.0002 (g). Data are shown as the mean ± SE in plots of all individual data (b–d, f, g) or as the mean ± SE in the spaghetti plot shown in Supplementary Fig. 1 (c).

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