Maintenance of the microvasculature improves thymus tissue structure and functions in aged mice

Age-related atrophy of the thymus plays a central role in the aging of the immune system, and interventions aiming at delaying thymus loss-of-function could improve the ability of the immune system to cope with infectious diseases and increase the effectiveness of vaccinations in the older population. We have recently shown that, in mice, age-associated vascular dysfunction, due to impaired VEGF signaling, is a high driver of the progressive deterioration of many other organs structure and function. Here we show that in aging mice, thymus involution correlates with a decreased microvascular density. VEGF supplementation by controlled overexpression in transgenic old mice significantly delays aging-associated microvascular rarefaction, loss of functional tissue and accumulation of fat cells in the thymus. The total number of CD4+ and CD8+ T cells population as well as naïve T cells and Recent thymic emigrants (RTE) was increased in VEGF old mice as compared to their wild type littermates. In culture, proliferation of T cells in response to anti-CD3 and anti-CD28 exposure was also significantly improved in splenocytes isolated from VEGF old mice and was comparable to the proliferation of T cells isolated from young mice. Controlled overexpression of a soluble form of the VEGF receptor inhibiting VEGF signaling in young adult mice, accelerated thymus tissue involution, accompanied by a decrease in total T cells, Naïve T cells and RTE numbers.

Our results support the concept that vascular aging plays an important role in age-related thymus atrophy and suggest counteracting VEGF signaling impairment as a tool to maintain proper thymus functions.