UCLA

Adult stem cells (ASCs), also known as somatic stem cells or tissue stem cells, are a tissue-resident population of cells that maintain tissue homeostasis and facilitate tissue repair. ASCs have the ability to self-renew and differentiate into mature cell types to replace damaged or lost cells. ASCs are in the driver’s seat when it comes to maintaining tissue homeostasis and function. Understanding the molecular regulators of ASC behavior is of great importance, and more specifically – how the molecular regulators are altered by age and disease. This study explores the intrinsic and extrinsic regulators of intestinal stem cells (ISCs).

ISCs are a specialized, multipotent population of ASCs that are responsible for maintaining homeostasis of the small intestine and colon. The intestine undergoes rapid cellular turnover; in some mammals, the intestinal epithelium is replenished every 3-5 days. ISCs are highly proliferative and have the ability to increase their production of progenitor cells to replace lost or damaged cells as a result of injury. ISCs reside within a highly regulated and protective niche that enables them to sustain tissue homeostasis. Disruptions to this niche or alterations of the molecular regulators of ISCs can compromise homeostasis, leading to impaired regeneration, tissue dysfunction, intestinal diseases, or the development of colorectal cancer.

This dissertation will explore how intrinsic and extrinsic factors regulate intestinal homeostasis through the lens of ISC function. We will demonstrate how aging impacts ISC behavior by identifying novel molecular pathways that contribute to age-related ISC dysfunction. We also demonstrate how exercise can be used to reverse age-related ISC dysfunction, while providing evidence of possible molecular mediators that are impacted by exercise. Furthermore, we examine the role of L1CAM in healthy mammalian intestinal tissue and assess how aging influences its expression and potential contribution to disease progression.