Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments

Abstract

Structural alterations in thymuses of female rats during the first 2 years of life were evaluated by morphometric analysis and, then, correlated with organization of epithelial cells in various thymic compartments, examined for their cytokeratin immunoreactivity. With an advancing age, the thymuses demonstrated morphological modifications related to maturation and senescence, the dynamics of which varied between particular thymic compartments, and involved subpopulations of thymic epithelial cells. In the entire period of life the most dynamic changes were found in the cortex while the medulla was demonstrated to be a rather "stable" region. Morphometric studies revealed a negative correlation between the volume of thymic cortex and medulla and age of rats and a linear, positive relationship between the volume of connective tissue compartment and age. Changes in organization of epithelial network in the medulla preceded those observed in the cortex. Decreased proliferative activity of subset of medullary cells, which probably represented a self-renewable population, was accompanied by alterations in the immunocytochemically characterized (cytokeratines) differentiation process. At the same period of life, hypertrophy and hyperplasia of superficial epithelial cells seems to functionally replace medullary cells. This process begins around 3rd month of life and expands on all thymic compartments. The first changes in the cortex appeared around 8th month and were connected with reduced cytokeratin immunoreactivity. The involution observed in older animals was preceded by age-related alterations in epithelial network pattern which, in the course of stable morphometric parameters (between 5th and 12th month), showed character of a structural and functional adaptation.

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

“…Our data are in accord with reports demonstrating age-related changes to thymic size and structure, including that of reduced Troma-I, which would result in decreased thymic output of mature naive T cells [3, 101]. Most significant age-related thymic changes often occur in the cortex, resulting in a negative correlation between thymic cortex, volume, and age [3]. As the thymic cortex hosts the earlier stages of thymic T cell development, its disruption in GIT2KO mice may contribute to disturbed T cell development.…”

“…GIT2 deletion thus seems to, in-part, engender thymic dysfunction via mechanism(s) linked to reductions in cellular survival support, as suggested by the loss of an appropriate T cell maturation environment due to the Troma-I reductions (Figure 2). Our data are in accord with reports demonstrating age-related changes to thymic size and structure, including that of reduced Troma-I, which would result in decreased thymic output of mature naive T cells [3, 101]. Most significant age-related thymic changes often occur in the cortex, resulting in a negative correlation between thymic cortex, volume, and age [3].…”

Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth

“…The data described above, as well as the findings of others (Steinmann et al , 1985; Brelinska et al , 2008; Li et al , 2003), suggest that the cortex plays a dominant role in thymic atrophy, and likewise dominates the regrowth response. We used our global transcriptional profiles of cortical stromal cells from young, aged, and regenerated thymuses to establish the molecular mechanisms of these processes.…”

“…Overall, our studies indicate that at a time (roughly mid-life) when atrophy is already quite substantial (~75% loss of cellularity), changes in stromal cells are predominant, with cortical stromal changes being the most obvious. A dominant effect of aging on the cortical compartment has been indicated by the data of others in mice, rats, and humans (Steinmann et al , 1985; Brelinska et al , 2008; Li et al , 2003; Sutherland et al , 2005), although restoration of cortical volume in the (transiently) regenerated thymus has not been reported.…”

Morphological and immunohistochemical characterisation of the thymus in juvenile turbot (Psetta maxima, L.)

“…However, further studies will be necessary to elucidate the functional implications of possible cell to cell interactions. Anti-CYT antibodies are the most common immunomarker used to define the thymus stroma in fish ) and mammals (Shezen et al 1995;Brelinska et al 2008). On the other hand, the SMA immunoreactivity described in RECs in this study has only been reported previously in the thymus of chicken and mammals (Drenckhahn et al 1978) and consequently the anti-SMA antibody constitutes a novel immunomarker for RECs in turbot.…”