Ageing, metabolism and the intestine

The intestinal epithelium serves as a dynamic barrier to the environment and integrates a variety of signals, including those from metabolites, commensal microbiota, immune responses and stressors upon ageing. The intestine is constantly challenged and requires a high renewal rate to replace damaged cells in order to maintain its barrier function. Essential for its renewal capacity are intestinal stem cells, which constantly give rise to progenitor cells that differentiate into the multiple cell types present in the epithelium. Here, we review the current state of research of how metabolism and ageing control intestinal stem cell function and epithelial homeostasis. We focus on recent insights gained from model organisms that indicate how changes in metabolic signalling during ageing are a major driver for the loss of stem cell plasticity and epithelial homeostasis, ultimately affecting the resilience of an organism and limiting its lifespan. We compare findings made in mouse andDrosophilaand discuss differences and commonalities in the underlying signalling pathways and mechanisms in the context of ageing.