Fig. 6: Inhibition of p38 MAPK rescues natural aging of mouse villi.

a Western blot results showed that 17.5-month-old mouse crypt samples displayed elevated MKK6 expression, increased p38 MAPK activation, and increased p53 and p16 levels, which were suppressed by RAP treatment for 1.5 months starting at 16 months of age. Right panel: quantification data (mean ± SEM). N = 3 mice per group. *P < 0.05, **P < 0.01 (determined using Student’s t test). b–d Inhibition of p38 MAPK largely rescued the deterioration in villus and crypt structures (b), decreased nutrient absorption activities (c), and compromised regeneration (d) in 17.5-month-old normal mice. The mice were treated with SB203580 for 1.5 months. Data are expressed as mean ± SEM. N = 5 mice per group. *P < 0.05, **P < 0.01 (determined using Student’s t test). e Representative images showing that SB203580 (2 μM) or RAP (0.5 μM) partially rescued the defects in growth and crypt formation of minigut organoids isolated from 17.5-month-old mice. The inhibitors were added to the culture at day 1 of the organoid cultures. Bottom panels: quantification data (mean ± SEM). N = 3 mice per group. **P < 0.01 (determined using Student’s t test). f Lgr5-CreERT;Mapk14^f/+ mice (TAM injected at 2 months of age) did not show aging-like villus structural defects at 16 months of age. The intestines were sectioned and stained with H/E or Ki67 antibodies. Right panels: quantification data (mean ± SEM). N = 5 mice per group. *P < 0.05, **P < 0.01 (determined using Student’s t test).