Figure 1.

Age-associated reduction in intestinal regeneration is caused by decreased function of Lgr5+ stem cells and the Paneth cell niche

a, Organoid forming capacity of human colonic crypts (n=24). Linear regression +/− 95% CI. Over 60 years old donors show significantly lower organoid-forming capacity (inset). b, Regenerative growth of crypts from old and young mice. Organoids derived from young mice (n=6) generate more de novo crypt domains (arrowheads) in primary cultures (5–9 days after isolation). Representative images from Day 7, Scale bar 50μm. Student’s paired t-test. c, Cellular frequencies analyzed by flow cytometry (n=30 young, n=26 old). For FACS gating strategy, see Supplementary Fig. 1. d, Clonogenicity of young and old Lgr5^hi stem cells co-cultured with young and old Paneth cells (n-values for analysed mice shown). Combinations compared to average of young Lgr5^hi cells co-cultured with young and old Paneth cells. Y = mice between 3 and 9 months of age, O = mice over 24 months of age in all experiments. Unless otherwise indicated, line at Box-and-Whisker -plots represents median, box interquartile range and whiskers range. All other data are represented as mean +/− s.d. and conditions compared with two-tailed unpaired Student’s t-test, exact P-values shown in corresponding panels. P-values < 0.05 were considered significant.