Fig. 3

miR-146a blocks the effect of metformin on the alleviation of aging in mice. a–f The miR-146a agomir attenuates the effect of metformin on aging prevention in a mouse progeria model. a Experimental design. Mice received intraperitoneal (i.p.) injection of D-gal (100 mg/kg/day) daily for 13 weeks to induce progeria. Metformin (100 mg/kg/day, i.p.) was administered to treat mice daily for 13 weeks with/without miR-146 agomir treatment. The miR-146a agomir (250 nmol/kg, intravenously [i.v.]) was administered to treat mice twice weekly for 4 weeks. b Representative images show that the miR-146a agomir blunted metformin effects on mouse hair phenotype changes. c, d The miR-146a agomir blunts metformin-induced increases in physical endurance and grip strength in D-gal-induced aged mice. c Physical endurance was measured by treadmill, the time before exhaustion was recorded (n = 5). d Grip strength was measured using a mouse-gripper meter (n = 10). e The miR-146a agomir inhibits metformin-induced reduction in liver senescence. Representative images of SA-β-gal staining of liver tissues are shown (n = 6). Scale bar, 100 μm. f The miR-146a agomir inhibits metformin-induced reductions in p16 protein levels in liver and lung tissues (n = 6). g–j The miR-146a antagomir shows comparable anti-aging effects as metformin in a mouse progeria model. g Experimental design. Mice were injected with D-gal (100 mg/kg/day, i.p.) daily for 13 weeks to induce progeria. Metformin (100 mg/kg/day, i.p.) was administered to treat mice daily for 13 weeks. The miR-146a antagomir (250 nmol/kg, i.v.) was administered to treat mice twice weekly for 4 weeks. h, i The miR-146a antagomir shows comparable effects on mouse physical endurance and grip strength as metformin in D-gal-induced aged mice (n = 6). h Physical endurance was measured by treadmill, and the time before exhaustion was recorded (n = 6). i Grip strength was measured using a mouse-gripper meter (n = 6). j The miR-146a antagomir shows comparable effects on p16 levels in liver and lung tissues of D-gal-induced aged mice (n = 6). *p < 0.05, **p < 0.01, ***p < 0.001