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

项目摘要/摘要 我们的目标是了解衰老时血小板(Plt)的产生和功能。Plts在以下方面发挥着重要作用 止血，防止出血的过程，也参与免疫调节。与老龄化相关 与血小板相关的疾病急剧增加，包括血小板数量的变化(血小板增多症或 血小板减少)和Plt活性。Plt的半衰期非常短，由 造血干细胞(HSC)。我们发现，Plt生产的分化路径是 幼鼠和老年鼠的情况有所不同。在这里，我们建议研究背后的分子和细胞机制。 衰老特有的分化途径，以及对Plt功能和衰老生理的影响。我们 假设衰老特异的Plt通路导致Plt相关风险的显著增加 老年人的精神障碍。我们发现了一种新的、特定于年龄的分化途径，为我们提供了一个独特的 缓解Plt相关疾病的新发现的机会，包括血栓形成和 心血管疾病，在老年人中。

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.