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. Author manuscript; available in PMC: 2023 Feb 22.
Published in final edited form as: Nat Metab. 2022 Jul 28;4(8):995–1006. doi: 10.1038/s42255-022-00609-6

Fig. 3 |. Senolytics blunts the ability of the aged circulation to induce senescence transfer in young kidney and liver tissues.

Fig. 3 |

a, Study design used in b–g. b, Venn diagram showing the overlap between up-regulated circulating SASP proteins identified in old versus young mice (>1.5-fold) and down-regulated proteins in vehicle (Veh)-treated versus DQ-treated old mice (<0.7-fold). c, List of overlapping proteins in b. d,e, Senescence/SASP-associated gene expression in kidney (d) and liver (e) of young mice receiving old blood treated with Veh (YO+Veh; n = 4) or DQ (YO+DQ; n = 6). f,g, Representative SA-β-gal staining (n = 5 for YO+Veh; n = 7 for YO+DQ; 10–15 images per mouse) and quantification of SA-β-gal+ cells per area in kidney (f) and liver (g) (n = 5 for YO+Veh; n = 8 for YO+DQ; 7–10 images per mouse). h, Study design used in i–p. i, Venn diagram showing the overlap between up-regulated circulating SASP proteins in old versus young mice (>1.5-fold) and down-regulated proteins in Veh-treated versus ABT263-treated old mice (<0.7-fold). j, List of overlapping proteins in i. k–l, Senescence/SASP-associated gene expression in kidney and liver of young mice receiving old blood treated with Veh (YO+Veh) or ABT263 (YO+ABT) (n = 6 per group). m,n, Representative images of SA-β-gal staining in kidney (n = 8 for YO+Veh; n = 7 for YO+ABT; 6–10 images per mouse) and quantification of SA-β-gal+ cells per area (m) and HMGB1+ tubular cells (n). Scale bar, 500 μm. o,p, Images of SA-β-gal staining in liver (n = 5 for YO+Veh; n = 6 for YO+ABT; ten images per mouse) and quantification of SA-β-gal+ cells per area (o), γ-H2AX foci (n = 5 per group; 6–8 images per mouse) and TUNEL+ hepatocytes (n = 4 for YO+Veh; n = 5 for YO+ABT; 5–9 images per mouse) (p). Scale bar, 100 μm. Two independent experiments were performed. Data are means ± s.e.m. of biologically independent samples. Statistical significance was calculated using multiple Mann–Whitney tests with a two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli, with Q = 5%, *q < 0.05 (d,e,k,l) and a two-tailed t-test with a Welch’s correction (f,g,m–p) with *P < 0.05; **P < 0.01; ***P < 0.001. Rel, relative.