ALTERED STEM-CELL REGENERATION IN IRRADIATED INTESTINAL CRYPTS OF SENESCENT MICE

Ageing is associated with a progressive deterioration in the functions of many organs within the body. In tissue with high cell turnover, th e maintenance of the stem cells is of particular importance. Any accum ulation of damage in stem cells may affect their function and hence th reaten the homeostasis and regenerative capacity of the tissue. The sm all intestine represents a good model for the study of stem cells beca use of its spatial and hierarchical organisation, We have examined the effect of age on stem cell regenerative capacity after irradiation, u sing the microcolony assay. Crypt survival levels, the growth rate of surviving crypts, and the number of cells able to repopulate a crypt h ave been investigated by irradiating groups of 6-7 month old and 28-30 month old ICRFa male mice, After high doses of irradiation, the survi ving crypts in old mice were both smaller and fewer in number than in young mice. The growth rate of surviving crypts was determined by meas uring the crypt area and the number of cells/crypt at various times af ter 14 Cy irradiation. There was a growth delay of between about one h alf and one day in the older mice. Surprisingly, the number of clonoge nic cells per crypt was estimated to be greater in the older mice, The se studies indicate important age-related alterations in the capacity to regenerate the crypts after radiation damage.