Defining the cause and consequence of aging-specific platelet specification from hematopoietic stem cells

项目总结/摘要 我们的目标是了解血小板（Plt）的生产和功能老化。Plts在以下方面发挥重要作用： 止血、防止出血的过程，还参与免疫调节。衰老与 血小板相关疾病的急剧增加，包括血小板数量的改变（血小板增多或 血小板减少症）和Plt活性。PLT的半衰期很短， 造血干细胞（HSC）。我们发现Plt产生的分化途径是 在年轻和年老的老鼠身上是不同的。在这里，我们建议调查背后的分子和细胞机制， 衰老特异性分化途径，以及Plt功能和衰老生理学的后果。我们 假设衰老特异性Plt通路导致Plt相关性血小板减少的风险显著增加， 老年人的疾病。我们发现了一种新的年龄特异性分化途径， 缓解Plt相关疾病（包括血栓形成和 老年人的心血管疾病

PROJECT SUMMARY/ABSTRACT Our goal is to understand platelet (Plt) production and function upon aging. Plts play essential roles in hemostasis, the process of preventing bleeding, and also participate in immune regulation. Aging is associated with a dramatic increase in platelet-related disorders, including alterations in Plt numbers (thrombocytosis or thrombocytopenia) and in Plt activity. Plts have a very short half-life and are continually produced by hematopoietic stem cells (HSCs). We have discovered that the differentiation pathways of Plt production are different in young and old mice. Here, we propose to investigate the molecular and cellular mechanisms behind the aging-specific differentiation path, and the consequences for Plt function and aging physiology. We hypothesize that the aging-specific Plt pathway contributes to the dramatically increased risk for Plt-related disorders in the elderly. Our discovery of a new, age-specific differentiation pathway provides a unique opportunity for novel discoveries towards mitigating Plt-related disorders, including thrombosis and cardiovascular disease, in the elderly.