Human Immunosenescence

Abstract

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.

Evidence of premature immune aging in patients thymectomized during early childhood

“…Together, these findings indicate that in order to cope with the strong pressure imposed by CMV, the cellular immune system prematurely exhausts its resources in the context of lack of adequate thymic output. Although CMV infection is usually considered benign, it has been proposed to play an important role in the development of immunosenescence (46). Our data highlight the impact of this virus on the immune system and potential consequences on immune integrity in particular contexts such as the absence of thymus.…”

No Immune Risk Profile among individuals who reach 100 years of age: Findings from the Swedish NONA immune longitudinal study

“…The increased numbers of centenarians in recent decades is mainly due to a dramatic decline in the mortality rate among those above 80-years of age (Jeune, 2002). The rate of mortality due to cardiovascular disease or cancer increases with age from middle age up to about 80 year old and levels off thereafter, whereas the mortality due to infectious disease continue to accelerate also in very late life (reviewed in Pawelec et al, 2006). The ageing human body is less able to cope with infectious disease probably due to changes in innate and especially adaptive immunity (Delarosa et al, 2006;Solana et al 2006).…”

Human Cytomegalovirus Gene Expression Is Silenced by Daxx-Mediated Intrinsic Immune Defense in Model Latent Infections Established In Vitro

“…Human cytomegalovirus (HCMV) is a betaherpesvirus that infects the majority of the population, causes severe disease in immunocompromised patients, is the leading viral cause of birth defects, and likely plays a role in age-related immunosenescence, certain cardiovascular diseases, and some cancers (12,64,70,77,78). A cellular component of PML nuclear bodies, the Daxx protein, confers intrinsic immunity against HCMV (8,72,79,91).…”