Grant: Project Grant

The human body is composed of ~50 trillion cells, most or all of which undergo a process of cell aging during our lifetimes. Many cell types such as skin or blood cells continue to divide throughout our lifetimes and when they have divided a certain number of times, they reach a point called cell senescence, where they cannot divide any further and become detrimental to the health of the body. A small proportion of our cells called stem cells largely avoid this cell aging process and contribute fresh cells to the body to maintain tissue and organ function. It is thought that replenishing the population of stem cells can slow the process of aging and rejuvenate particular tissues and organs, to maintain health at advanced age. Experiments to test this idea have been previously done in different tissues of animal models, with experiments in mice making up the majority of studies. We have made a unique mouse model in which the animals initially appear normal but the number of stem cells is reduced in several tissues examined. In this application we propose to allow our animals to age naturally, and then see whether their brain stem cells are reduced or absent in a part of the brain where stem cells are usually found. We will also test their memory to see if reduction of their stem cells reduces maintenance of memory. In parallel we will examine the tissues and organs of the mice to see if there are obvious deficits in their function, and if so what features of the cells and tissues are compromised. These studies will determine the contribution of stem cells to maintaining health and normal tissue and organ function. We predict that some tissues that show rapid cell growth like those in the skin would show the greatest effect and provide insight into how it might be possible to extend healthy function of different tissues and organs into old age.