Hematopoietic stem cell function and regeneration are often impaired with age, creating a chronic immunosuppressed state, increasing susceptibility to disease and preventing the effective delivery of many critical treatments like chemotherapy or radiation. The experiments proposed are designed to define the mechanisms that maintain normal stem cell function and that are compromised during aging and to develop effective approaches to circumvent this critical problem. These studies are important because a better understanding of how stem cell function changes with age and the ability to activate cellular and molecular elements may improve hematopoietic function during aging.
Developing new approaches to effectively reverse the decline in health that is associated with aging can be a challenging task. The experiments proposed here have broad implications in this regard, and will not only define a critical pathway associated with the age-related decline in stem cell self-renewal and function, but will seek to reverse this decline by identifying pathways that can be targeted to enhance the regenerative potential and functional capacity of stem cells. These studies are critical because they have the potential to fundamentally transform treatment strategies for a wide variety of diseases and conditions that afflict the elderly, including chronic immunosuppression, cancer and degenerative disorders, which would be a direct benefit to all citizens in the State of California.