胸腺退化
自身免疫
蛋白质稳态
表观遗传学
免疫学
免疫衰老
炎症
衰老
T细胞
获得性免疫系统
幼稚T细胞
表型
生物
神经科学
免疫系统
T细胞受体
遗传学
基因
作者
Marı́a Mittelbrunn,Guido Kroemer
标识
DOI:10.1038/s41590-021-00927-z
摘要
The aged adaptive immune system is characterized by progressive dysfunction as well as increased autoimmunity. This decline is responsible for elevated susceptibility to infection and cancer, as well as decreased vaccination efficacy. Recent evidence indicates that CD4+ T cell–intrinsic alteratins contribute to chronic inflammation and are sufficient to accelerate an organism-wide aging phenotype, supporting the idea that T cell aging plays a major role in body-wide deterioration. In this Review, we propose ten molecular hallmarks to represent common denominators of T cell aging. These hallmarks are grouped into four primary hallmarks (thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, and loss of proteostasis) and four secondary hallmarks (reduction of the TCR repertoire, naive–memory imbalance, T cell senescence, and lack of effector plasticity), and together they explain the manifestation of the two integrative hallmarks (immunodeficiency and inflammaging). A major challenge now is weighing the relative impact of these hallmarks on T cell aging and understanding their interconnections, with the final goal of defining molecular targets for interventions in the aging process. In this Review, Mittelbrunn and Kroemer propose that ten molecular hallmarks represent the common denominators of T cell aging.
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