Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space

According to the remodeling theory of aging we proposed several years ago, the current data on human immunosenescence depicts a complex scenario where clonotypical immunity deteriorates, while ancestral innate/natural immunit y is largely conserved or even up-regulated with age. Under an evolutionary perspective, antigens are the cause of a persistent life-long antigenic st ress, responsible for the accumulation of effector CD8+/CD28- T cells, the decrease of naive T cells (CD95-) and the marked shrinkage of T cell repert oire with age. Concomitantly, NK cytotoxicity, chemotaxis, phagocytosis and complement activities remain unaffected or negligibly affected, in compari son to clonotypical immunity. Thus, immunosenescence is not a random deteri orative phenomenon but appears to inversely recapitulate an evolutionary pa ttern. On the whole, immunosenescence can be envisaged as the result of the continuous challenge of the unavoidable exposure to a variety of potential antigens (viruses, bacteria, but also food and self molecules among others ). From this perspective antigens are nothing else than a particular type o f stressor and immunosenescence appears to be the price paid to immunologic al memory, i.e. one of the main characteristics of the most evolutionary re cent and sophisticated type of immunity. Together with the age-related thym ic involution, and the consequent age-related decrease of thymic output of new T cells, this situation leaves the body practically devoid of virgin T cells, and thus likely more prone to a variety of infectious and non infect ious diseases. (C) 2000 Elsevier Science Ltd. All rights reserved.