11 April 2025
Lucy O'Brien
Department of Molecular and Cellular Physiology
Stanford University School of Medicine
Healthy organs are often described as maintaining "tissue homeostasis" – a dynamic equilibrium between cell division and loss that preserves cell number, fates, and organ size. Deviations from this balance are commonly seen as forerunners of cancer or degeneration. I will argue that, contrary to this view, homeostatic deviations are a natural feature of robust organ health: Many mature organs reversibly change size and composition to optimize function upon changing physiological demand. I will discuss how this "tissue allostasis" creates a landscape of metastable organ states, how flux through cell lifecycles underlies allostatic plasticity, and how coupling of cell lifecycles in tissue neighborhoods defines organ size. Understanding the basis of allostatic control may suggest tunable treatments for dysregulated cellular flux in disease.