Understanding ageing of the thymus

The thymus is the organ devoted to T cell differentiation, maturation and export to the periphery. Unique among organs, the thymus undergoes multiple rounds of natural atrophy and redevelopment. Atrophy of the thymus, also known as involution, is temporally induced by stress stimuli, ranging from infection to pregnancy, and chronically induced during healthy aging. The genetic and structural control over age-related thymic involution is poorly understood, despite the influence the phenomenon has on the peripheral T cell pool.

We investigated the FVB/N mouse strain, which displays premature thymic involution. FVB mice have multiple structural and architectural features that precede thymic involution, with the division of the thymus into discrete lobules and disruption of the relationship between thymic epithelial cells and the vasculature responsible for the importation of hematopoietic precursors. Correlated with the disruption of the epithelium-endothelium relationship was a reduction in precursor thymocytes, providing a potential mechanism for thymic involution. These structural features, reminiscent of the human thymus, are intrinsic to the non-hematopoietic compartment and are controlled by weak polygenic loci. These results suggest a series of developmental steps that may precede thymic involution during aging.

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Michelle Linterman
Brian Heap Room