Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY/ABSTRACT The goal of this proposal is to understand the mechanisms regulating platelet (Plt) production and function upon aging. Plts play essential roles in hemostasis, the process of preventing bleeding. Aging is associated with a dramatic increase in platelet-related disorders, including alterations in Plt numbers (thrombocytosis or thrombocytopenia) and in Plt hyperreactivity. Plts have a very short half-life of only a few days and are therefore continually produced by hematopoietic stem cells (HSCs). HSCs are long-lived and undergo a number of molecular and functional changes with age; thus, we postulate that Plt aging is a consequence of properties inherited by their long-lived HSC source. Excitingly, we have discovered that the differentiation pathways of Plt production are different in young and old mice. We hypothesize that the aging-specific Plt pathway contributes to the dramatically increased risk for Plt-related disorders in the elderly. Here, we propose to investigate the molecular and cellular mechanisms driving the aging-specific differentiation path, and the consequences for Plt function and aging physiology. Our discovery of a new, age-specific differentiation path from HSCs to Plts provides a unique opportunity for novel discoveries towards mitigating Plt-related disorders, including thrombosis and cardiovascular disease, in the elderly.
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