Reactive Oxygen Species in intestinal stem cell metabolism, fate and function

Long dismissed as merely harmful respiratory by-products, Reactive Oxygen Species (ROS) have emerged as critical intracellular messengers during cell growth and differentiation. ROS's signaling roles are particularly prominent within the intestine, whose high regenerative capacity is maintained by Intestinal Stem Cells (ISCs). In this review, we outline roles for ROS in ISCs as revealed by studies using Drosophila and mouse model systems. We focus particularly on recent studies highlighting how ROS ties to metabolic adaptations, which ensure energy supply matches demand during ISC activation and differentiation. We describe how declines in these adaptive mechanisms, through aging or pathology, promote reciprocal changes in ISC metabolism and ROS signaling. These changes ultimately contribute to aberrant ISC function, a loss of tissue homeostasis, and a shortened lifespan. • Reactive Oxygen Species (ROS) control Intestinal Stem Cell (ISC) fate and function. • Moderate ROS promote ISC activation and tissue renewal. • Excessive ROS drive ISC hyperplasia, apoptosis and tissue dysfunction. • Modulation of ROS can rejuvenate the intestine and extend lifespan.