Chronic inflammation and aging: DNA damage tips the balance

被引：79

作者：

Cavanagh, Mary M. ^{[1
,2
]}

Weyand, Cornelia M. ^{[1
,2
]}

Goronzy, Joerg J. ^{[1
,2
]}

机构：

[1] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[2] Palo Alto Vet Adm Hlth Care Syst, Dept Med, Palo Alto, CA 94304 USA

来源：

CURRENT OPINION IN IMMUNOLOGY | 2012年 / 24卷 / 04期

基金：

美国国家卫生研究院;

关键词：

HEMATOPOIETIC STEM-CELLS; TOLL-LIKE RECEPTORS; CD8(+) T-CELLS; RHEUMATOID-ARTHRITIS; B-CELLS; IMMUNE; ANTIGEN; AGE; EXPRESSION; INFECTION;

D O I：

10.1016/j.coi.2012.04.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The aged immune system, typically hyporesponsive to infection and vaccination, can be hyperresponsive in the context of inflammatory pathology. Here we review current work examining the mechanisms behind the amplified inflammatory profile of aged adaptive immunity, and the reciprocal relationship between chronic inflammation and immune aging. Aged hematopoietic stem cells are driven to differentiate following accumulated DNA damage, thus depleting the stem cell pool and increasing the number of damaged effector cells in the circulation. Chronic DNA damage responses in lymphocytes as well as senescent cells of other lineages initiate the production of inflammatory mediators. In addition, aged lymphocytes become less reliant on specific antigen for stimulation and more prone to activation through innate receptors. When these lymphocytes are exposed to inflammatory signals produced by senescent tissues, the bias toward inflammation exacerbates destruction without necessarily improving immunity.

引用

页码：488 / 493

页数：6

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