Impacts of hematopoietic stem cell aging on distant tissues

About This Grant

Project Summary Aging is a degenerative process resulting in the functional decline across organs. How organs interact to coordinate the aging process is largely unknown, but this knowledge is important in understanding the increasing prevalence of dysfunctions in multiple organs and multi-morbidities with aging. Recent human studies have shown that somatic mutations accumulate in hematopoietic stem cells (HSCs) over time, resulting in expansion of mutated blood cells and a higher risk for not only blood diseases but also myocardial infarctions, strokes, vascular complications of type 2 diabetes, and earlier mortality. These observations suggest that changes in HSCs may impact the functions of distant tissues. In this proposal, we will test the hypothesis that because the blood system supports all tissues, HSC aging can manifest in their progeny and therefore affect distant tissues and organismal aging. We have established a mouse model that reverses HSC aging. We will characterize this mouse model for healthspan and lifespan and decipher the molecular and cellular changes that underlie the alteration in healthspan and lifespan. This proposal is significant because it will address whether and how HSC aging impacts the functions of distant tissues and organismal aging, and improve our understanding of how organs interact to coordinate the aging process. The unique mouse models we have generated provide an opportunity to address this question. Clinic ready compounds will be tested for reversing the effects of HSC aging on tissue functions and organismal aging.