TY - JOUR
T1 - Chronic inflammation and aging
T2 - DNA damage tips the balance
AU - Cavanagh, Mary M.
AU - Weyand, Cornelia M.
AU - Goronzy, Jörg J.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health ( U19 AI 57266 and U19 AI090019 to JJG, and R01 AR42527 , R01 EY11916 , R01 AI44142 and P01 HL058000 to CMW.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.coi.2012.04.003
DO - 10.1016/j.coi.2012.04.003
M3 - Review article
C2 - 22565047
AN - SCOPUS:84865304528
SN - 0952-7915
VL - 24
SP - 488
EP - 493
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
IS - 4
ER -