Impaired intestinal cell proliferation parallels increased senescence after burn injury in aged mice

The global population is aging, with one in six people projected to be 65 years or older by 2050. Since people aged 65 and older experience higher rates of morbidity and mortality after burn injury, there is an increased need to develop effective burn treatments in this age group. Heightened morbidity and risk of mortality may stem from increased gut leakiness and death of intestinal epithelial cells of aged individuals. Herein, we used our clinically relevant model of scald burn injury in young and aged mice to ascertain whether the colon, isolated colonic epithelium, and organoids grown from the colon, have deficiencies in cell growth, senescence, and apoptosis pathways. Aged, burn-injured mice displayed increased senescence marker cdkn2a in the colon and isolated epithelium, and displayed a reduction in proliferation marker cdk4 in the colon when compared to young mice. Changes in senescence and proliferation coincided with a reduction in stem cell marker lgr5 in the colon and colonic epithelium, suggesting a burn-related reduction in the stemness of the epithelial crypt. While we failed to see histological changes in the colonic epithelium, we observed an increase in pro-apoptotic cleaved caspase 3 and 9 within the colons of aged, burn-injured mice. Finally, there was a decrease in the expression antimicrobial peptide ang4, and not camp in the colons of aged, burn-injured mice. Taken together, these data suggest that in the colon, disruption of proliferation and apoptosis in aged burn-injured mice occurs primarily in the non-epithelial compartment.