Mechanisms of immunosenescence: lessons from models of accelerated immune aging
Article first published online: 6 JAN 2012
© 2012 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1247, The Year in Immunology pages 69–82, January 2012
How to Cite
Le Saux, S., Weyand, C. M. and Goronzy, J. J. (2012), Mechanisms of immunosenescence: lessons from models of accelerated immune aging. Annals of the New York Academy of Sciences, 1247: 69–82. doi: 10.1111/j.1749-6632.2011.06297.x
- Issue published online: 31 JAN 2012
- Article first published online: 6 JAN 2012
- immune aging;
- thymic involution;
With increasing age, the ability of the adaptive immune system to respond to vaccines and to protect from infection declines. In parallel, the production of inflammatory mediators increases. While cross-sectional studies have been successful in defining age-dependent immunological phenotypes, studies of accelerated immune aging in human subpopulations have been instrumental in obtaining mechanistic insights. The immune system depends on its regenerative capacity; however, the T cell repertoire, once established, is relatively robust to aging and only decompensates when additionally stressed. Such stressors include chronic infections such as CMV and HIV, even when viral replication is controlled, and autoimmune diseases. Reduced regenerative capacity, chronic immune activation in the absence of cell exhaustion, T cell memory inflation, and accumulation of highly potent effector T cells in these patients synergize to develop an immune phenotype that is characteristic of the elderly. Studies of accelerated immune aging in autoimmune diseases have identified an unexpected link to chronic DNA damage responses that are known to be important in aging, but so far had not been implicated in immune aging.