Thymic involution in aging

Abstract

The size of the naive T-cell pool is governed by output from the thymus and not by replication. This pool contributes cells to the activated/memory T-cell pool whose size can be increased through cell multiplication; both pools together constitute the peripheral T-cell pool. Aging is associated with involution of the thymus leading to a reduction in its contribution to the naive T-cell pool; however, despite this diminished thymic output, there is no significant decline in the total number of T cells in the peripheral T-cell pool. There are, however, considerable shifts in the ratios of both pools of cells, with an increase in the number of activated/memory T cells and the accumulation in older individuals of cells that fail to respond to stimuli as efficiently as T cells from younger individuals. Aging is also associated with a greater susceptibility to some infections and some cancers. An understanding of the causal mechanism of thymic involution could lead to the design of a rational therapy to reverse the loss of thymic tissue, renew thymic function, increase thymic output, and potentially improve immune function in aged individuals.