Longevity and the immune response

Abstract

The domino hypothesis of the onset of age associatedimmune insufficiency suggests that it is theconsequence of a cascade of events beginning withinvolution of the thymus. Involution is associatedwith a reduced thymic output leading to fewernaïve T cells contributing to the peripheral T-cell pool. Homeostatic mechanisms, which maintain thenumber of T cells in the peripheral pool withinprecise limits, induce the proliferation and prolongthe survival of resident T cells to fill the nichesleft vacant by the absent naïve T cells. In thishypothesis, falling thymic output would be matched byresident T-cell proliferation and with age theseproliferating cells will reach their replicativelimit. Their prolonged survival will lead to theaccumulation of cells unable to replicate, producinga decline in immune function and a susceptibility toinfection, or certain cancers.Comparison of gender differences in life-span andrates of death in each age group due to infectious orparasitic disease suggests that the immune system infemales works more efficiently and effectively forlonger than the immune system in males. This leads tothe suggestion that involution of the thymus, andhence thymic output, occurs more rapidly in males thanin females.