Fig. 5: ASC division rates are inversely proportional to lifespan and positively associated with somatic mutation rates.

a Regression analysis showing a positive correlation between Lgr5^+CBC cell division rates per year determined by BrdU labelling and Ki67 positivity in NMR (left) and mouse (right) small intestine and colon. Each data point represents the mean value of 30 crypts counted per animal and the shaded area represents 95% confidence interval of the regression line. P-values and R² from two-tailed F-tests and correlation coefficients (r) are indicated on the graphs. b Bar graphs showing mean percentage (±SEM) of proliferation index of rodent Lgr5^+CBC or human LGR5^+CBC cells across different ages in NMRs (n = 3 animals/age group) (left), mice (n = 3 animals/age group) (middle) and humans (n = 4 individuals in 28 to 33-years-old age group, n = 5 in 65 to 70-years-old and n = 5 in 71 to 74-years-old group) (right). P-values from two-tailed Wilcoxon rank-sum tests are indicated on the graphs. c Left, allometric regression of division rates of colonic ASCs at the crypt base (Lgr5^+CBC or LGR5^+CBC) on lifespan. Mean division rates of small intestinal Lgr5^+CBC cells in mice and NMRs (black triangles) are also shown but have not been included in the least-square fit. Right, regression of division rates of colonic Lgr5⁺ or LGR5⁺ cells located above the crypt base on lifespan. Mean division rates of small intestinal Lgr5⁺ above crypt base cells in mice and NMRs (black triangles) are also shown but have not been included in the least-square fit. Red triangles represent mean colonic Lgr5⁺ cell division rates (n = 3 animals/species) or LGR5⁺cell division rates in humans (n = 2 individuals taken from Ishikawa et al.³¹).The shaded area represents the 95% confidence interval of the regression line. P-values and R² by two-tailed F-tests and correlation coefficients (r) are indicated on the graphs. d Allometric regression of substitution rates³² on cell division rates of colonic ASCs (Lgr5^+CBC or LGR5^+CBC) cells. Red triangles indicate mean substitution rates taken from Cagan et al.³² and the shaded area represents 95% confidence interval of the regression line. P-values and R² by two-tailed F-test and correlation coefficients (r) are indicated.