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. 2020 Aug 27;11:4289. doi: 10.1038/s41467-020-18039-x

Fig. 6. Senolytics decrease the number of senescent cells, reduce cf-mt-DNA levels, alleviate systemic inflammatory immune response after IRI, and prolong cardiac allograft survival.

Fig. 6

a Old C57/B6 mice were treated with senolytics (D and Q, or either D or Q in b) on 3 successive days/week. After 1 month, kidney, heart, and skin were procured, stained, and the percentage of senescent cells assessed as described in Fig. 4, (p = 0.0079); Column plots display mean ± SD, (n = 5 biologically independent animals). b Systemic levels of p16Ink4a and cf-mt-DNA were measured by real-time PCR and calculated relative to GAPDH expression (old vs. old + D and Q: p = 0.0317); Column plots display mean ± SEM, (n = 6 biologically independent animals). c Young and old C57BL/6 mice were treated with senolytics for 3 successive days/week for 1 month. Subsequently, IRI was induced in young and old animals; IL-17 and IFN-γ expression of CD4+ and CD8+ T cells were assessed by flow cytometry (old control vs. old treated: CD4+IL-17+ (p = 0.0087)/CD4+IFN-γ+ (p = 0.0022)/CD8+IFN-γ+ (p = 0.0022); column plots display mean ± SD, (n = 6 biologically independent animals). d Old and young donor C57BL/6 mice were treated with D and Q or PBS prior to fully mismatched cardiac transplantation and allograft survival was monitored by daily palpation (p = 0.0012); (n = 8 biologically independent animals). e Old and young donor C57BL/6 mice were treated with D and Q or PBS prior to fully mismatched cardiac transplantation while recipient animals were treated with weekly injections of CTLA4-IG following transplantation and allograft survival was monitored by daily palpation (p = 0.0064); (n = 5 biologically independent animals). Results are representative of at least three independent experiments. Statistical significance was determined by two-tailed Mann–Whitney test. Survival was compared by log-rank Mantel–Cox test. Asterisks indicate p values *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001, ****p ≤ 0.0001, only significant values are shown. Source data are provided as a Source Data file.