Human immunosenescence: does it have an infectious component?

• Published in: Annals of the New York Academy of Sciences Vol. 1067; no. 1; pp. 56 - 65
• Main Authors: Pawelec, G, Koch, S, Franceschi, C, Wikby, A
• Format: Journal Article
• Language: English
• Published: United States 01-05-2006
• Subjects: Aged; Aging; Aging - immunology; Animals; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus - pathogenicity; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Cytomegalovirus Infections/immunology/virology; Cytomegalovirus/immunology/pathogenicity; Humans; Immunity - immunology; Longitudinal Studies; Models, Immunological; SARS coronavirus; Models; Immunological
• ISSN: 0077-8923; 1749-6632; 1749-6632
• DOI: 10.1196/annals.1354.009

The rate of acceleration of the frequency of death due to cardiovascular disease or cancer increases with age from middle age up to around 75-80 years, plateauing thereafter. Mortality due to infectious disease, however, does not plateau, but continues to accelerate indefinitely. The elderly are particularly susceptible to novel infectious agents such as SARS, as well as to previously encountered pathogens. Why is this? The elderly commonly possess oligoclonal expansions of T cells, especially of CD8 cells, which, surprisingly, are associated with cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the same phenotypic and functional alterations to T cell immunity that have been suggested as biomarkers of immune system aging. We suggest that, in fact, CMV, not age per se, is the prime driving force behind many or most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells in the elderly. Thus, the manner in which CMV and the host immune system interact (over which period? on which genetic background? with which co-infections?) is critical in determining the "age" of adaptive immunity and hence human longevity. In this respect, immunosenescence is infectious.