Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load

Under an evolutionary perspective, antigens can be considered nothing else than chronic stressors that constituted the major selective pressure for im mune system emergence and evolution. In this review, recent data are discus sed under the hypothesis that human immunosenescence is the consequence of the continuous attrition caused by chronic antigenic overload/stress. The a dvantage of this theoretical approach is that a unifying hypothesis is prop osed, which tries to Fill in the current gap between the conceptualizations concerning the mechanisms which counteract aging and favor longevity in in vertebrates and vertebrates. The hypothesis is that the immune system is, a t a higher level of biological organization and complexity, the counterpart of the anti-stress response network identified in invertebrates as the maj or determinant of survival. We argue that some of the most important charac teristics of immunosenescence, i.e. the accumulation and the clonal expansi on of memory and effector T cells, the reduction/exhaustion of naive T cell s, and the shrinkage of T cell repertoire, are compatible with this assumpt ion. Thus, immunosenescence can be envisaged as a global reduction of the " immunological space." Concomitantly, immunosencscence results in the progre ssive generation of cellular mosaicism which is the consequence of the hete rogeneous replicative histories and telomere shortening of T and B cell sub sets, as well as hemopoietic stern cells. Most of the parameters affected b y immunosenescence appear to be under genetic control, and future research on biomarkers should address this point. On the whole, immunosenescence can be taken as a proof that the beneficial effects of the immune system, devo ted to the neutralization of dangerous/harmful agents early in life and in adulthood, rum to be detrimental lace in life, in a period largely not fore seen by evolution. This perspective fits with basic assumptions of evolutio nary theories of aging, such as antagonistic pleiotropy. (C) 1999 Elsevier Science Inc. All rights reserved.