Several distinct lines of ongoing (but unfortunately poorly funded) research aim to restore at least some degree of youthful activity to the thymus in old individuals, and researchers here demonstrate one of them: a process of introducing young thymus cells into an old thymus. The thymus plays a vital role in the generation of immune cells, and during childhood the rate of production is high. In early adulthood the thymus atrophies in a process known as involution, however, and the supply of new immune cells diminishes to a trickle. This is one of the important limiting constraints that determine the way in which the immune system ages. Restoring an old thymus should improve immune function in adults, and given that the degeneration of immune function in the old is a large component of the frailty of old age, this is an important and much underrated goal.
The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery after bone marrow transplantation. Although several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known.
Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells (TECs) to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony-forming assays reveal that the engraftment and proliferative capacities of TECs diminish early in life, whereas the receptivity of the thymus to TEC engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell-intrinsic changes in the proliferative capacity of TECs, and further show that young TECs can engraft and directly drive the growth of involuted thymuses.