Human immunosenescence: is it infectious?

Abstract

Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age-associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is also all too apparent for common pathogens such as influenza. Many years ago, it was noted that the elderly possessed oligoclonal expansions of T cells, especially of CD8(+) cells. At the same time, it was established that cytomegalovirus (CMV) seropositivity was associated with many of the same phenotypic and functional alterations to T-cell immunity that were being reported as biomarkers associated with aging. It was discovered that CMV was the prime driving force behind most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells. Independently, longitudinal studies of a free-living population of the very old in Sweden over the past decade have led to the emerging concept of an 'immune risk phenotype' (IRP), predicting mortality, which was itself found to be associated with CMV seropositivity. These findings support our hypothesis that the manner in which CMV and the host immune system interact is critical in determining the IRP and hence is predictive of mortality. In this sense, then, we suggest that immunosenescence is contagious.

Telomerase and the aging process

“…One aspect should be mentioned, and that is that overall changes in telomere length could be the result of changes in subsets of cells. In this context it is of interest that expansion of blood CD8 + T lymphocytes is associated with all-cause mortality (Wikby et al, 2002;Pawelec et al, 2005). CD8 + CD28 − T lymphocytes have telomeres that are shorter than those of other white blood cells from the same individual (Monteiro et al, 1996;Effros et al, 1996); this may be connected to the observation that loss of CD28 expression is also associated with loss of ability of T lymphocytes to upregulate telomerase activity (Valenzuela and Effros, 2002).…”

Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily

“…Importantly, later longitudinal studies in Sweden, examining a representative sample of the very elderly not selected for good health, the majority of whom were actually frail, revealed that the IRP, including CMV seropositivity, still predicted mortality (Pawelec et al, 2005). More recent studies using this longitudinal "NONA" population, now over 90 yr of age, suggested that the number of different clones expanding in the elderly, and particularly the later clonal attrition observed to occur in IRP individuals, was highly correlated with 2, 4 and 6 year survival in this population (Hadrup et al, 2006).…”

“…Huppert et al, 2005) we asked whether CMV had an over-riding effect on specific immunity in this population as well. We also examined a second persistent herpes virus, EBV, which was known to have a similar, but lesser effect, in the Swedish population (Pawelec et al, 2005).…”

The extreme longevity: The state of the art in Italy

“…Some of the most important characteristics of clonotypic immunity in ageing are compatible with this assumption since it is characterized by a decrease of virgin T cells and by the filling up of the immunological space by "megaclones" of memory T cells, resistant to apoptosis and capable of exerting negative regulatory functions (Franceschi et al, 2000a;De Martinis et al, 2005;Pawelec et al, 2004Pawelec et al, , 2005. Concomitantly, the antigenic load results in the progressive generation of inflammatory responses involved in agerelated diseases, for which the name "inflamm-aging" has been proposed (Franceschi et al, 2000c).…”