Longevity and the immune response

Abstract

The domino hypothesis of the onset of age associated immune insufficiency suggests that it is the consequence of a cascade of events beginning with involution of the thymus. Involution is associated with a reduced thymic output leading to fewer naïve T cells contributing to the peripheral T-cell pool. Homeostatic mechanisms, which maintain the number of T cells in the peripheral pool within precise limits, induce the proliferation and prolong the survival of resident T cells to fill the niches left vacant by the absent naïve T cells. In this hypothesis, falling thymic output would be matched by resident T-cell proliferation and with age these proliferating cells will reach their replicative limit. Their prolonged survival will lead to the accumulation of cells unable to replicate, producing a decline in immune function and a susceptibility to infection, or certain cancers. Comparison of gender differences in life-span and rates of death in each age group due to infectious or parasitic disease suggests that the immune system in females works more efficiently and effectively for longer than the immune system in males. This leads to the suggestion that involution of the thymus, and hence thymic output, occurs more rapidly in males than in females.