Figure 7. HMM-HA improves the maintenance of ISCs during ageing.

a. Representative pictures of LGR5 in situ hybridization in the small intestine of young and old nmrHas2 and creER mice. Scale bar, 50 μm.

b. Lgr5+ intestinal stem cell counts in the small intestines of 7- and 24-months old mice. Pooled females and males (n=10).

c. Intestinal crypts isolated from nmrHas2 mice have significantly upregulated Has2 levels. Intestinal crypts were isolated from 5-months old mice (n=4).

d. Intestinal crypts from old nmrHas2 mice form more intestinal organoids in vitro n=3. Addition of HMM-HA, but not LMM-HA, to creER crypts resulted in a greater number of organoids. Scale bar, 100 μm.

e. Organoid quantification in 7- and 24-months old mice (n=3).

f. Model for the anti-ageing effects of HMM-HA. HMM-HA produced by overexpression of the nmrHas2 gene protects tissues from oxidative stress, improves maintenance of ISCs to provide a better gut barrier function during ageing and reduces the production of pro-inflammatory molecules by immune cells. The beneficial effects of HMM-HA further contribute to the longevity and healthspan of the mice. For b, c and e, P values were calculated using two-tailed unpaired t-tests; P values are indicated in the graphs. For b, c and e, data are mean ± s.e.m. The symbols represent biological replicates. Adjustments were made for multiple comparisons.