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Thymus Shrinkage Contributes to Atherosclerosis


Today, we want to highlight a study that shows the link between atherosclerosis and the age-related shrinking of the thymus, which is arguably the most important organ of the immune system [1].

The adaptive and innate immune systems and atherosclerosis

The thymus is essentially like an army base where new T cells develop and are trained to become the soldiers of the adaptive immune system. However, as we age, the thymus shrinks, its ability to train new T cells declines, and the immune cell-producing tissue turns to fat and slowly wastes away; this process is known as thymic involution.

This loss of thymic output results in a decline of the adaptive immune system; the immune system can no longer mount an effective defense and is inappropriately activated, causing chronic inflammation and widespread dysfunction.

However, atherosclerosis is more closely associated with the innate immune system and a type of cell that has little to do with the thymus: the macrophage. Macrophages are the waste clearers of the immune system, and in the case of atherosclerosis, they identify cholesterol deposits in arterial walls and attempt to remove them.

Unfortunately, macrophages become less able to remove such deposits with age, and an increasing number of them become trapped and die in the process of attempting to remove them. The result is an increasing mountain of dead and dying macrophages, which build up over time, causing inflammation; they are the basis of the arterial plaques associated with atherosclerosis.

So, what is the link between these two seemingly separate systems? Chronic inflammation appears to be the link here. The authors make the interesting hypothesis that low-density lipoprotein and the age-related decline of thymic function create a feedback loop that facilitates the progression of atherosclerosis.

Atherosclerosis is considered as an immune inflammatory disease, and the T cell-mediated immune inflammatory response plays an important role in the pathogenesis of atherosclerosis. T cells mature in the thymus site and are involved in the process of atherosclerosis induced by inflammation and immune response. Inflammatory mechanisms and immune system mechanisms are crucially involved in the pathophysiology of atherosclerosis and cardiovascular disease. T lymphocytes are involved and play an important role in both the inflammatory response and the immune response. An imbalance of the degree of activation of the protective Treg lymphocytes, the pro-inflammatory and cytotoxic macrophages and T-effector lymphocytes could thus be at the origin of the triggering or not of progression of vascular injury. However, all of these processes are closely associated with thymus function. In other words, changes in the function of thymus will be deeply affecting the process.

Based on previous research, we can speculate that the changes of thymus function may have an impact on the process of atherosclerosis. The mechanism of thymus involvement in the process of atherosclerosis is assumed as follows: Low density lipoprotein or cholesterol reduces the expression of the thymus transcription factor Foxn1 via low density lipoprotein receptors (LDLR) on the membrane surface and low density lipoprotein receptor-related proteins on the cell surface, which cause the thymus function decline or degradation. The imbalance of T cell subgroups and the decrease of naive T cells due to thymus dysfunction cause the increase or decrease in the secretion of various inflammatory factors, which in turn aggravates or inhibits atherosclerosis progression and cardiovascular events. NK T cell, DCs and macrophages can affect the process of atherosclerosis by affecting the production of naive T cells through the thymus. Furthermore, these cells can also participate in the progression of atherosclerosis via the direct secretion of cytokines or inducing other cells to secrete cytokines.

According to our hypothesis, lentiviral transfection, siRNA, gene knockout and thymic transplantation technologies can be selected to improve aging thymus function in animal experiments. In the clinical treatment of atherosclerosis, and even other immune-related diseases, we may consider using a vaccine, or a similar alternative to foxn1 to improve the expression of foxn1 in the human body, thereby improving or restoring aging thymus function and resisting the related-diseases caused by the decline of immunity.

In summary, novel data increasingly suggests the potential for new targets of the thymus function for therapeutic intervention to modify the course and reduce events in atherosclerosis and cardiovascular disease, as studies increasingly implicate thymus-related mechanisms. Further investigation on changes of thymus function will help to develop new therapeutic targets that may improve outcomes in atherosclerosis and cardiovascular disease and discover novel approaches in the treatment of atherosclerosis and vascular disease.


This is yet more support for thymic rejuvenation being a priority when it comes to combating age-related diseases and ill health. There are several current efforts towards achieving this; you may find this interview with Dr. Grey Fahy of interest in this regard, as he is currently developing a method of regrowing the human thymus.


[1] Dai, X., Zhang, D., Wang, C., Wu, Z., & Liang, C. (2018). The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response. International journal of medical sciences, 15(13), 1555.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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