Organ homeostasis and regeneration are facilitated by multipotent tissue stem cells that give rise to all the mature cell types of a specific organ. During an organism’s life, adult stem cell pools are maintained by cell division requiring both the genome and the epigenome to be faithfully copied. However, according to the relatively few studies conducted to date, changes in the epigenome and in consequence gene expression can be detected in a large number of aged organs/tissues. The intestinal epithelium is an ideal model to study ageing as it constitutes a high-turn-over tissue that is renewed every 4-5 days. Epigenetic changes are likely to accumulate in the intestinal stem cell (ISC) pool due to its high rate of cell division, and indeed age-related changes in DNA methylation status were shown for whole organ preparations. Coincidentally, incidence of certain types of cancer (e.g. colorectal cancer) also increase with age, moreover alterations of the epigenome have been suggested to be the underlying causes. Age related changes also impact on functional properties of the intestinal epithelium as evidenced by a reduced capacity to take up essential nutrients like calcium and phosphorus. Combining fluorescent reporter genes and surface markers we have been able to extract ISCs in large numbers (up to 3*105 cells per animal). When embedded in matrigel, intestinal crypts or single ISCs can be cultured in vitro and give rise to so called organoids, intestinal structures with crypt and villus-like epithelial domains that contain ISCs, transit amplifying cells and all differentiated cell types. In order to study the effect of ageing on the ISC niche in detail we have performed immunohistochemical characterisation of tissue sections, functional in vitro assays and expression profiling of the stem cell compartment in mice of different age groups (1.5 month, 10 months, 24 months). Our results show clear changes in intestinal morphology, expression profile and regeneration potential. To further investigate the underlying causes for these functional and transcriptional changes, we are currently studying how different epigenetic modifications in ISCs are altered during aging.