Fig. 4: EVs secreted by senescent BMMs propagate senescence and aging, whereas YBMM-EVs partially rejuvenate aging.
a, Experimental setup for EV transplantation. BMMs were isolated from young mice (3 months old, male) and aged mice (20 months old, male), and EVs secreted by BMMs were collected (YBMM-EVs, ABMM-EVs) and subsequently transplanted into young recipients (3 months old, male mice). b, Immunofluorescence staining for p53 in muscle (scale bar, 50 μm; n = 4 mice) (upper left), adipose tissue (scale bar, 50 μm; n = 4 mice; 5–6 images per mouse) (middle left) and bone sections (scale bar, 50 μm; n = 6 mice; 5–6 images per mouse) (bottom left) of young mice treated with YBMM-EVs or ABMM-EVs, and their quantitative analysis (right). c, GTT and ITT were performed on young mice receiving adaptive transfer of EVs (n = 6 mice). d, Phosphorylation level of insulin signaling in liver (left) and quantitative analysis (right) (n = 3 mice). e, Representative µCT images (n = 6 mice). f, Outline of the studies. BMMs were isolated from young mice (3 months old, male) and aged mice (20 months old, male), and EVs secreted by BMMs (YBMM-EVs, ABMM-EVs) were collected and subsequently transplanted into aged recipients (20 months old, male mice). g, Immunofluorescence detection of p53 in liver (upper left) and femur (middle left) (scale bar, 50 μm; n = 4 mice; 5–6 images per mouse) and γH2A.X in muscle (scale bar, 50 μm; n = 4 mice; 5–6 images per mouse) (lower left) and brain (scale bar, 50 μm; n = 5 mice; 5–6 images per mouse) (bottom left) of aged mice after YBMM-EV or ABMM-EV transplantation, and their quantitative analysis (right). h, Protein levels of senescence-related markers in liver (upper left), muscle (middle) and adipose tissue (upper right), and their quantitative analysis (bottom) (n = 3 mice). i,j, GTT (i) and ITT (j) (n = 5 mice). The colored shading in c, i and j represents the area under the curve. k, Representative µCT images (left) and quantitative analysis (right) of bone volume/tissue volume (BV/TV) (n = 5 mice). Data are presented as mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001 and #P < 0.0001, as determined by one-way ANOVA followed by Tukey’s multiple comparison test. mo, months;
