Macaulay Richard, Akbar Arne N, Henson Sian M
Division of Infection and Immunity, Rayne Institute, University College London, 5 University Street, London, WC1E 6JF, UK.
Age (Dordr). 2013 Jun;35(3):563-72. doi: 10.1007/s11357-012-9381-2. Epub 2012 Jan 15.
Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is highlighted by their being predictors of earlier mortality. We have recently published that the proinflammatory cytokine TNFα is a strong inducer of CD4(+) T-cell senescence and T-cell differentiation, adding to the growing body of literature implicating proinflammatory molecules in mediating these critical age-related T-cell alterations. Moreover, the inflammatory process is also being increasingly implicated in the pathogenesis of many common and severe age-related diseases, including cancer, cardiovascular diseases and type 2 diabetes. Furthermore, major age-related risk factors for poor health, such as obesity, stress and smoking, are also associated with an upregulation in systemic inflammatory markers. We propose the idea that the ensuing inflammatory response to influenza infection propagates cardiovascular diseases and constitutes a major cause of influenza-related mortality. While inflammation is not a negative phenomenon per se, this age-related dysregulation of inflammatory responses may play crucial roles driving age-related pathologies, T-cell immunosenescence and CMV reactivation, thereby underpinning key features of the ageing process.
衰老伴随着T细胞免疫的改变以及一种称为炎症衰老的低度慢性炎症状态。这些现象的重要性体现在它们是早期死亡的预测指标。我们最近发表的研究表明，促炎细胞因子TNFα是CD4(+) T细胞衰老和T细胞分化的强烈诱导剂，这进一步增加了越来越多的文献表明促炎分子在介导这些与年龄相关的关键T细胞改变中的作用。此外，炎症过程也越来越多地涉及许多常见和严重的与年龄相关疾病的发病机制，包括癌症、心血管疾病和2型糖尿病。此外，与健康状况不佳相关的主要年龄相关风险因素，如肥胖、压力和吸烟，也与全身炎症标志物的上调有关。我们提出这样的观点，即随后对流感感染的炎症反应会引发心血管疾病，并构成流感相关死亡的主要原因。虽然炎症本身并非负面现象，但这种与年龄相关的炎症反应失调可能在驱动与年龄相关的病理、T细胞免疫衰老和巨细胞病毒再激活方面发挥关键作用，从而支撑衰老过程的关键特征。
