Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Alzheimer's Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Ageing Res Rev. 2024 Nov;101:102540. doi: 10.1016/j.arr.2024.102540. Epub 2024 Oct 10.
Age-related changes initiate a cascade of cellular and molecular alterations that lead to immune system dysfunction or abnormal activation, predisposing individuals to age-related diseases. This phenomenon, commonly referred to as immunosenescence, highlighting aging-associated progressive decline of the immune system. Moreover, mounting evidence suggests that immunosenescence contributes to a related pathological phenomenon known as inflammaging. Inflammaging refers to chronic, low-grade, and systemic inflammation associated with aging, occurring despite the absence of overt stimuli. In the body, inflammation is typically activated in response to overt stimuli such as bacterial/microbial invasion or a pathological state, however, inflammaging occurrence and its underpinning mechanisms seem to be independent and in the absence of such stimuli. Despite recent advancements in molecular characterization and the scrutiny of disease relevance, these two interconnected concepts have remained largely unexplored and unrecognized. In this comprehensive review, we aim to shed light on the mechanistic and cellular aspects of immunosenescence and inflammaging, as well as their pivotal roles in the pathogenesis of aging-related diseases, including cancer, infections, dementia, and neurodegenerative disorders.
年龄相关的变化引发了一系列细胞和分子的改变，导致免疫系统功能障碍或异常激活，使个体易患与年龄相关的疾病。这种现象通常被称为免疫衰老，强调了与年龄相关的免疫系统逐渐衰退。此外，越来越多的证据表明，免疫衰老导致了一种与年龄相关的病理现象，即炎症衰老。炎症衰老指的是与衰老相关的慢性、低度和全身性炎症，尽管没有明显的刺激因素存在。在体内，炎症通常是在细菌/微生物入侵或病理状态等明显刺激下被激活的，然而，炎症衰老的发生及其潜在机制似乎是独立的，没有这些刺激因素的存在。尽管近年来在分子特征描述和疾病相关性方面取得了进展，但这两个相互关联的概念在很大程度上仍未得到探索和认识。在这篇全面的综述中，我们旨在阐明免疫衰老和炎症衰老的机制和细胞方面，以及它们在与年龄相关的疾病发病机制中的关键作用，包括癌症、感染、痴呆和神经退行性疾病。
