Adult stem cells maintain tissues for the life of an organism by balancing regeneration with tissue damage and turnover. Accordingly, the functional decline associated with aging is hypothesized to result from the reduced net stem cell function. Mechanisms that increase stem cell number, maintenance, or function could therefore be used to counter age related tissue damage. Surprisingly, the very properties that set stem cells apart from all other cells have not been studied extensively in the context of aging. I will study whether the stem cell niche, or asymmetric cell division have roles in aging.
Stem cells are surrounded by the niche cells that provide stem cells with factors regulating proliferation and differentiation. I have discovered that the intestinal stem cell niche couples stem cell function to the organismal nurient status during Calorie Restriction (CR) and increases stem cell number via a paracrine mechanism. As CR extends the lifespan and inhibits aging related phenotypes in multiple organisms, I will investigate whether niche mediated mechanisms can oppose the functional decline of the aging intestine.
Stem cells generate two daughter cells with distinct fates in asymmetric cell division. It is conceivable that stem cells may asymmetrically apportion old and damaged cellular material to the differentiating progeny to secure the stem cell lineage. I have developed a method to address the age dependent apportioning of organelles in cell division, and discovered that the mammary progenitor cells dispose certain organelles age-dependently to the differentiating daughter. I will determine the role of this new mechanism in stem cell biology and aging.
Call for proposal
See other projects for this call