Extended Data Fig. 8: MiR-378a and miR-191 regulate age-related dysfunction.
a, The mRNA levels of FASN and ACC1 in liver of young recipients transplanted with macrophage-miR-378a-EVs (n = 4 mice). b, The mRNA levels of senescence-related markers in liver (n = 6 mice for AAV-Control; n = 5 mice for AAV-F4/80-Cre). c, Protein levels of senescence markers in muscle and adipose tissue of miR-378a-BMM-CKO mice (n = 3 mice). d, The AUC data of GTT and ITT (n = 6 mice for AAV-Control; n = 5 mice for AAV-F4/80-Cre). e, Phosphorylation levels of insulin signaling in adipose tissue (n = 3 mice). f, Expression levels of G6Pase, PEPCK, FASN and ACC1 in the liver (n = 6 mice for AAV-Control; n = 5 mice for AAV-F4/80-Cre). g, Immunohistochemical staining of osteocalcin in femurs of aged mice injected with AAV-miR-191 (scale bar, 50μm; n = 6 mice). h, Immunohistochemical staining of p21 in femurs of young mice injected with AAV-F4/80-miR-191-sponge (scale bar, 50μm; n = 6 mice). i, Hanging endurance and grip strength (n = 6 mice). j, The mRNA levels of senescence-related markers in primary hepatocytes after miR-378a overexpression (n = 6 biological replicates for miR-378a mimic; n = 3 biological replicates for other groups). k, The mRNA levels of senescence-related markers in primary hepatocytes after inhibition of miR-378a expression (n = 4 biological replicates for miR-378a inhibitor; n = 3 biological replicates for other groups). l-m, Representative images of SA-β-gal staining in primary hepatocytes (scale bar, 300μm; n = 5 biological replicates for miR-378a inhibitor; n = 3 biological replicates for other groups), and their quantitative data. n, The mRNA levels of senescence-related markers in BMSCs after miR-191 overexpression (n = 3 biological replicates). o, Representative images of SA-β-gal staining in BMSCs (n = 3 biological replicates). Data are shown as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; #P < 0.0001 were determined using two-tailed t-test in b (Cdkn2a, Il-1β and Il-6), c-i and o, two-tailed t-test with a Welch’s correction in b (Cdkn1a and Tnf-α) and one-way ANOVA followed by Tukey’s multiple comparison test in a, j-n.
