Intestinal stem cells heterogeneity and clonal dominance during aging: two faces of the same coin?

Intestinal epithelium undergoes dysfunctions and diseases over time with an exponential increase in the elderly population. Recent studies reported that the intestinal stem cells (ISCs) show a functional decline during aging and a lack of an appropriate cell identity control. Increase of cell-to-cell heterogeneity is a hallmark of aging tissues and organs, however there is little experimental evidence with regard to the cell heterogeneity of the ISCs. On the other hand, the ISCs continuously experience a niche clonality process that diminishes the initial cell heterogeneity over time. In this review, we discuss the latest findings on these topics focusing on the potential mechanisms driving intestinal stem cell heterogeneity and clonality during aging.