Thymus Atrophy in Middle Age

Researchers here present data for excess weight to accelerate the involution of the thymus, a process that is no doubt sensitive to mechanisms such as the increased inflammation that accompanies obesity. The thymus is an organ in the chest, the destination for thymocytes created in the bone marrow. Thymocytes mature into T cells of the adaptive immune system over a period of weeks in the thymus. Unfortunately, active thymus tissue is progressively replaced by fat over the course of adult life. A good fraction of middle-aged people have negligible tissue remaining, and thus a negligible supply of new T cells. Without reinforcements, the adaptive immune system steadily collapses into a collection of senescent, malfunctioning, exhausted cells, incapable of fending off pathogens or clearing harmful senescent or potentially cancerous cells.

Fatty degeneration of thymus (or thymus involution) has long been considered a normal ageing process and the role of thymus in adults has drawn little attention. However, there is emerging evidence that thymic involution is linked to T cell aging, chronic inflammation, and increased morbidity. Other factors than chronological age have been proposed to affect the involution rate. However, thymus involution and its determinants have been little studied at a general population level.

In the present study, we investigated the imaging characteristics of thymus on computed tomography (CT) in a Swedish middle-aged population. In total, 1,048 randomly invited individuals (aged 50-64 years, 49% female) were included and thoroughly characterized. CT evaluation of thymus included measurements of attenuation, size, and a 4-point scoring system. A majority, 615 (59%) showed complete fatty degeneration, 259 (25%) predominantly fatty attenuation, 105 (10%) half fatty and half soft-tissue attenuation, while 69 (6.6%) presented with a solid thymic gland with predominantly soft-tissue attenuation.

Age, male sex, high BMI, abdominal obesity, and low dietary intake of fiber were independently associated with complete fatty degeneration of thymus. Also, fatty degeneration of thymus as well as low CT attenuation values were independently related to lower proportion of naïve CD8+ T cells, which in turn was related to lower thymic output, assessed by T-cell receptor excision circle (TREC) levels. In conclusion, among Swedish middle-aged subjects, nearly two-thirds showed complete fatty degeneration of thymus on CT.

Link: https://doi.org/10.21203/rs.3.rs-2499784/v1