Chronic inflammation and aging: DNA damage tips the balance

• Published in: Current opinion in immunology Vol. 24; no. 4; pp. 488 - 493
• Main Authors: Cavanagh, Mary M, Weyand, Cornelia M, Goronzy, Jörg J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2012
• Subjects: adaptive immunity; Allergy and Immunology; Animals; antigens; Cellular Senescence - physiology; Chronic Disease; DNA Damage; Humans; Immune System - physiology; Immunity; inflammation; Inflammation - immunology; lymphocytes; Lymphocytes - immunology; receptors; stem cells; tissues; vaccination
• ISSN: 0952-7915; 1879-0372; 1879-0372
• DOI: 10.1016/j.coi.2012.04.003

► The aging immune system is more prone to inflammation but less protective. ► DNA damage reduces stem cell renewal, depleting lymphoid and promoting myeloid progenitors. ► Poor DNA repair perpetuates damage and alters mature lymphocyte function. ► Aged T and B lymphocytes are less antigen-dependent and more inflammatory. ► Cytokine production by senescent cells exacerbates inflammation. 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.