Extended Data Fig. 6: EVs secreted by senescent BMMs propagate senescence, whereas young BMM-derived EVs ameliorate aging-related phenotypes of aged mice.
a, The electron microscopy analysis (scale bar, 100 nm) and particle size of EVs (n = 3 mice). b, The uptake of EVs by multiple tissues (n = 3 mice). c, Protein levels of senescence markers in multiple tissues of young mice treated with YBMM-EVs or ABMM-EVs (n = 4 mice for YBMM-EVs; n = 5 mice for ABMM-EVs). d, Immunohistochemical staining of p53 in muscle and adipose tissue (scale bar, 50μm; n = 4 mice). e-f, Immunofluorescence staining for γH2A.X in bone sections, and the quantitative analysis (scale bar, 50μm; n = 5 mice). g, AUC data of GTT and ITT were calculated respectively (n = 6 mice). h, Expression levels of G6Pase, PEPCK, PGC-1a, FASN and ACC1 in the liver (n = 4 mice). i, The LW/BW were measured in young recipients (n = 5 mice). j, Serum triglyceride (TG) levels (n = 5 mice for Y-control and YBMM-EVs; n = 4 mice for ABMM-EVs). k, Phosphorylation levels of insulin signaling in muscle and adipose tissue (n = 3 mice). l, Osteocalcin immunohistochemical staining of femoral bone sections (scale bar, 50μm; n = 6 mice). m, Quantitative analysis of trabecular bone related parameters (BV/TV) (n = 6 mice). n, Immunofluorescence detection of p21 in muscle of aged mice after treatment with YBMM-EVs or ABMM-EVs (scale bar, 50μm; n = 4 mice; 5 ~ 6 images per mouse). o, Representative images of p21 immunohistochemistry in adipose tissue (scale bar, 50μm; n = 4 mice). p, The AUC data of GTT and ITT (n = 5 mice). q, Immunohistochemical staining of osteocalcin in femurs (scale bar, 50μm; n = 5 mice). r, Nissl staining in brain (scale bar, 50μm; n = 5 mice; 5 ~ 6 images per mouse). Data are expressed as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; #P < 0.0001 were determined using two-tailed t-test in c. and one-way ANOVA followed by Tukey’s multiple comparison test in d-r.
