虽然年龄可以精确定义,高龄的临床表现在个体之间以不同的方式和不同的速率发生。观察到的高龄表型可能反映了几种生物衰老机制的叠加,随着世界对人口老龄化的争夺,这些机制已引起越来越多的关注。即使在免疫系统中,有多种与年龄相关的生物学机制在起作用,包括端粒功能障碍,表观遗传失调,免疫衰老程序,和线粒体功能障碍。这些生物学机制与临床综合征有关,如端粒功能障碍导致短端粒综合征(STS),最佳的患者管理可能需要识别基于生物学的衰老综合征。在肺移植的临床背景下,选择免疫衰老机制尤为明显。的确,STS越来越被认为是肺移植的适应症。同时,常见的衰老表型可能是由移植的压力引起的,因为肺同种异体移植物面临强大的免疫反应,需要更高水平的免疫抑制和相关的毒性,相对于其他实体器官。肺移植加剧的年龄相关疾病包括骨髓抑制,疱疹病毒感染,肝硬化,低球蛋白血症,脆弱,和癌症风险。本文旨在剖析免疫衰老的分子机制,并描述其在肺移植中的临床表现。虽然这些机制更有可能在肺移植中表现出来,这种基于机制的免疫衰老临床综合征方法与老年医学具有广泛的相关性。
While chronologic age can be precisely defined, clinical manifestations of advanced age occur in different ways and at different rates across individuals. The observed phenotype of advanced age likely reflects a superposition of several biological aging mechanisms which have gained increasing attention as the world contends with an aging population. Even within the immune system, there are multiple age-associated biological mechanisms at play, including telomere dysfunction, epigenetic dysregulation, immune senescence programs, and mitochondrial dysfunction. These biological mechanisms have associated clinical syndromes, such as telomere dysfunction leading to short telomere syndrome (STS), and optimal patient management may require recognition of biologically based aging syndromes. Within the clinical context of lung transplantation, select immune aging mechanisms are particularly pronounced. Indeed, STS is increasingly recognized as an indication for lung transplantation. At the same time, common aging phenotypes may be evoked by the stress of transplantation because lung allografts face a potent immune response, necessitating higher levels of immune suppression and associated toxicities, relative to other solid organs. Age-associated conditions exacerbated by lung transplant include bone marrow suppression, herpes viral infections, liver cirrhosis,
hypogammaglobulinemia, frailty, and cancer risk. This review aims to dissect the molecular mechanisms of immune aging and describe their clinical manifestations in the context of lung transplantation. While these mechanisms are more likely to manifest in the context of lung transplantation, this mechanism-based approach to clinical syndromes of immune aging has broad relevance to geriatric medicine.