Speaker: Jason Butler, University of Florida vice chief of research, hematology/oncology, and professor of medicine; and adjunct professor of medical sciences in the Center for Discovery and Innovation - HMH

Title: "Suppression of inflammaging prolongs hematopoietic healthspan"

Abstract: Average life expectancies have increased significantly, and the elderly population is growing with unprecedented speed worldwide. Within the US, it is estimated that by 2035, individuals over 65 years old will outnumber individuals under the age of 18 (23.9% versus 19.8% respectively). To minimize the financial and health impacts of aging on society, it will be critical to identify the mechanisms that contribute to the negative consequences associated with aging. Chronic low-grade inflammation observed in older adults, termed inflammaging, is a common feature underlying a multitude of aging-associated maladies including a decline in hematopoietic activity. However, whether suppression of inflammaging can preserve hematopoietic healthspan remains unclear, in part due to lack of tools to measure inflammaging within hematopoietic stem cells (HSC). Utilizing physiological and pre-mature aging models, we identified Thrombospondin-1 (Thbs1) as an essential regulator of inflammaging. We describe a transcriptomics-based approach for measuring inflammaging within stem cells and demonstrate that deletion of Thbs1 is sufficient to prevent inflammaging of HSC. Additionally, we have found that endothelial- and hematopoietic-specific deletion of Thbs1 are necessary for the phenotypes observed in global Thbs1 knockouts. Finally, we have extended these findings to the human hematopoietic system. Our results demonstrate that suppression of HSC inflammaging prevents aging-associated defects in hematopoietic activity including loss of HSC self-renewal and myeloid-biased differentiation. Our findings indicate that suppression of HSC inflammaging may also prolong overall systemic healthspan.

Hosts: Raquel Espin Palazon and Clyde Campbell, assistant professors in genetics, development and cell biology