University of Utah Molecular Medicine Program.
Department of Internal Medicine, University of Utah.
Curr Opin Hematol. 2019 Sep;26(5):336-342. doi: 10.1097/MOH.0000000000000526.
Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions that also mediate inflammatory responses and neurological diseases. These functions are relevant to disease processes prevalent among older adults and likely influence susceptibility to thrombotic and inflammatory disorders.
Platelet counts decrease in aged individuals whereas platelet reactivity increases. The platelet transcriptome is altered in aged individuals resulting in altered platelet function and exaggerated inflammation. Platelet signaling to monocytes in aging results in significantly more cytokines because of increased platelet-derived granzyme A. Platelet activation in aging appears to be driven, in part, because of increased reactive oxygen species and activation of the mammalian target of rapamycin pathway. Increased platelet hyperactivity in diseases is associated with aging, such cardiovascular disease and sepsis, exaggerate inflammation and thrombosis. Noncanonical functions of platelets influence the development of neurological diseases including Alzheimer's disease.
Although there have been advances dissecting the molecular mechanisms regarding aging-related changes in platelets, many knowledge gaps still remain. Studies filling these gaps are likely to identify new mechanisms driving aging-related changes in platelet gene expression and function, and contributing to injurious thrombo-inflammation in older adults.
血小板是一种专门的效应细胞，能够迅速对血管损伤部位做出反应。然而，新出现的数据表明，血小板具有多种功能，也可以介导炎症反应和神经疾病。这些功能与老年人中常见的疾病过程有关，可能会影响血栓形成和炎症性疾病的易感性。
血小板计数在老年人中减少，而血小板反应性增加。老年人的血小板转录组发生改变，导致血小板功能改变和炎症加剧。由于血小板源性颗粒酶 A 的增加，血小板向单核细胞的信号转导导致细胞因子显著增加。衰老过程中血小板的激活部分是由于活性氧的增加和哺乳动物雷帕霉素靶蛋白途径的激活所致。在疾病中，血小板过度活跃与衰老有关，如心血管疾病和败血症，会加剧炎症和血栓形成。血小板的非典型功能会影响包括阿尔茨海默病在内的神经疾病的发展。
尽管在解析与血小板衰老相关变化的分子机制方面已经取得了进展，但仍存在许多知识空白。填补这些空白的研究可能会确定新的机制，这些机制会驱动与衰老相关的血小板基因表达和功能的改变，并导致老年人的损伤性血栓炎症。
