Extended Data Fig. 6: SGLT2 inhibition affects PD-L1 expression by senescent cells.

a, FACS analysis for PD-L1 expression in irradiation-induced senescent HUVEC after 6 hours of AICAR treatment (n = 3 each). b, FACS analysis for PD-L1+ SPiDERβ-gal+ cells in stromal vascular fraction (SVF) obtained from gonadal white adipose tissue (gWAT) of high-fat diet (HFD) with or without canagliflozin (Cana) (n = 5, 7) on day 3. c, FACS analysis for immune cells in spleen and bone marrow of mice as prepared in Fig. 3a (n = 5 each). d, Protocol of the experiments to test the effects of CD3-neutralizung antibody on the senolytic effects of canagliflozin. NC, normal chow; HFD, high-fat diet. e, SA-β-gal activity in gWAT of mice as prepared in Extended Data Fig. 6d (n = 5, 4, 6, 5). f, FACS analysis of Matrigel transplantation model containing senescent fibroblasts (IR+) or non-senescent fibroblasts (IR–) (n = 5 each). IR, irradiation. Data were analyzed by two-way ANOVA followed by Tukey’s multiple comparison test (a, c, e) or two-tailed unpaired Student’s t-test (b, f). *P < 0.05, **P < 0.01. Exact P-value: Non-senescent+PBS versus Senescent+PBS: 0.0001, Senescent+PBS versus Senescent+AICAR: 0.0223 (a); HFD versus HFD+Cana3d: 0.0462 (PD-L1+ SPiDER+ cell) (b); NC versus HFD: 0.1075 (Spleen-T cell), 0.0503 (Spleen-CD8+ T cell), 0.0039 (BM-Myeloid) and 0.002 (BM-Lymphoid), HFD versus HFD+Cana: 0.0219 (T cell), 0.0345 (CD8+ T cell), 0.0328 (CD69+CD8+ T cell), 0.0433 (BM-Myeloid) and 0.062 (BM-Lymphoid) (c); HFD+contIgG versus HFD+Cana+contIgG: 0.0024, HFD+Cana+contIgG versus HFD+Cana+CD3εAb: 0.0405 (e); and Non-senescent versus Senescent: < 0.0001 (f). Data are shown as the mean ± SE in plots of all individual data (a–c, e, f). Gating strategy in FACS analysis was shown in Supplementary Fig. 3a (b), d (f), e (a), f (c), and g (c).

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