Intestinal stem cells (ISCs) are among the stem cells in the body with the highest rate of proliferation, which make them an excellent model to study different biological aspects like normal tissue homeostasis, aging, regeneration and cancer. It is thought that aging of ISCs might be linked to clinical phenotypes of the digestive tract ranging from malabsorption to cancer. There are reports highlighting the role of Lgr5+ stem cells in intestinal cancer supporting stem cell cancer (CSC) model. Our research focusing to investigate clonal evolution and heterogeneity of ISCs upon aging through different experimental approaches to obtain novel insight in the role of ISCs for aging and cancer. I addition we trying to find whether the ISC niches have a role in the clonality and heterogeneity of the ISCs up on aging and consequently the aging clinical phenotypes like cancer.