Bauer Moisés E, Wieck Andrea, Petersen Laura E, Baptista Talita S A
Laboratory of Immunosenescence, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Ann N Y Acad Sci. 2015 Sep;1351:11-21. doi: 10.1111/nyas.12786. Epub 2015 May 5.
Aging continuously remodels the immune system, a process known as immunosenescence. Here, we review evidence of premature immunosenescence in younger individuals under conditions of chronic psychological stress, chronic inflammation, or exposure to certain persistent viral infections. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic-pituitary-adrenal axis and increased cortisol levels. Chronic stress is associated with thymic involution, blunted T cell proliferation, increased serum proinflammatory markers, and shorter telomere lengths. Human cytomegalovirus (CMV) infection has been implicated in accelerating immunosenescence by shrinking the T cell receptor repertoire and causing clonal expansion of senescent CD8(+) CD28(-) T cells with a proinflammatory profile. These factors increase inflammation associated with aging, or "inflammaging," particularly as it relates to etiology of several age-related diseases and increased mortality. Patients with rheumatoid arthritis have been shown to have several signatures of premature immunosenescence, including expansion of senescent T cells associated with cognitive impairment. We end by speculating that bipolar disorder can be considered as a model of accelerated aging because it has been associated with shortened telomeres, higher CMV IgG titers, and expansion of senescent and regulatory T cells.
衰老不断重塑免疫系统，这一过程被称为免疫衰老。在此，我们综述了在慢性心理应激、慢性炎症或接触某些持续性病毒感染的情况下，较年轻个体中过早免疫衰老的证据。慢性应激可能通过激活关键的应激适应系统，特别是下丘脑 - 垂体 - 肾上腺轴并提高皮质醇水平，来加速免疫衰老的各种特征。慢性应激与胸腺萎缩、T细胞增殖减弱、血清促炎标志物增加以及端粒长度缩短有关。人巨细胞病毒（CMV）感染被认为通过缩小T细胞受体库和导致具有促炎特征的衰老CD8(+)CD28(-) T细胞的克隆扩增来加速免疫衰老。这些因素增加了与衰老相关的炎症，即“炎症衰老”，特别是与几种年龄相关疾病的病因和死亡率增加有关。类风湿性关节炎患者已被证明具有过早免疫衰老的若干特征，包括与认知障碍相关的衰老T细胞扩增。我们最后推测双相情感障碍可被视为加速衰老的模型，因为它与端粒缩短、更高的CMV IgG滴度以及衰老和调节性T细胞的扩增有关。
