Today, we are going to take a look at a new study in which scientists at the Walter and Eliza Hall Institute of Medical Research have recently identified a type of cell that appears to be implied in thymic involution—the shrinking of the thymus.
Thymic involution is somewhat of a mystery in biology, a phenomenon that isn’t fully understood that happens to everyone with age and is a driving cause of immunosenescence, the age-related decline in our immune systems’ ability to fight disease. This new study helps to shed light on why it happens.
What is the thymus?
The thymus is a tiny organ located right behind your collarbone, and it is an essential part of your immune system. In the thymus, undifferentiated thymocytes develop into naive T cells—immune cells that eventually specialize against specific pathogens or even cancer cells.
The thymus is fully developed before you’re even born; it is at that time, and in your early life, that it operates at peak performance. Thymic involution begins as early as the first year and continues through aging. This process causes thymic tissue to be gradually replaced with fat cells, reducing its ability to produce new naive T cells.
Past age 65, our ability to generate new naive T cells, and thus fight off new threats, is pretty much non-existent, leaving us open to infectious diseases and making vaccines less effective[2-4]. If it’s any consolation, this phenomenon is observed in most vertebrates.
Why does involution occur?
As of yet, there’s no universally accepted explanation why the thymus starts deteriorating so early on, but various hypotheses have been suggested.
One possibility is that thymic involution may be an effect of antagonistic pleiotropy—a phenomenon that selects genes whose benefits early in life outweigh costs late in life. Since the thymus is in charge of making sure that T cells are capable of telling foreign pathogens from the host—so that they won’t attack the body itself—it makes for a good target for any microbial parasites that could fool the immune system into thinking they’re harmless. Once they’ve snuck into the thymus undetected and set up shop, they might be able to overcome the immune system by simply preventing the now-contaminated thymus from producing more T cells that might be able to fight off the infection.
This might explain why the thymus is already working full tilt before you’re even born, producing lots of long-lived T cells while you’re being protected by your mother’s immune system and before you’re exposed to pathogens.
However, genes that favor a highly efficient thymus so early on might come with the caveat of early involution as well. This trait may have stuck with us because evolution normally favors genes that promote health up until reproductive age over genes that promote health past that point.
Other hypotheses are that early involution may help avoid autoimmunity, select for an optimal T-cell pool, and better allocate the limited resources available to the body.
Shedding light on thymic involution
In the new study, Dr. Daniel Gray and Dr. Julie Sheridan have identified a particular type of cell that may be involved in the involution of the thymus. As we age, the thymus increasingly turns into a mass of fat cells; this new research could help to explain why.
The research team has identified a stromal progenitor, a type of cell that can transform into several other types of cells, and in the thymus, stromal progenitors readily change into fat cells. The team believes that these cells play a key role in steadily replacing healthy, functioning immune tissues with fat. Eventually, the thymus is taken over by fat cells, and the production of T cells grinds to a halt.
Unlocking the secrets of why these progenitors favor changing into fat cells as we age could be important in turning back the clock in the thymus, helping to keep us disease-free. If we can manipulate these cell populations to support the creation of immune cell-producing tissue rather than becoming fat, this could potentially regenerate the thymus, helping older people to fight infections more effectively.
Being able to regenerate the thymus also has potential applications for bone marrow transplant patients and cancer patients whose immune systems have been weakened and need replenishing. There is also the potential for the treatment of primary immunodeficiencies and other rare conditions.
If you’d like to learn more about possible ways to restore thymic function, you may enjoy our interview with Dr. Greg Fahy, who is working on the rejuvenation of the thymus.
If we can figure out how and why involution happens, it may lead to ways to stop and hopefully even reverse it, decreasing the risk of infections and cancers in the elderly or otherwise immunodeficient patients. This study has brought us one step closer to understanding this process and one step closer to a solution.
 Sheridan, J. M., Keown, A., Policheni, A., Roesley, S. N., Rivlin, N., Kadouri, N., … & Gray, D. H. (2017). Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate Adipocytes, but Not Epithelial Cells. Cell reports, 21(4), 934-942.
 Taub, D. D., & Longo, D. L. (2005). Insights into thymic aging and regeneration. Immunological reviews, 205(1), 72-93.
 Naylor, K., Li, G., Vallejo, A. N., Lee, W. W., Koetz, K., Bryl, E., … & Goronzy, J. J. (2005). The influence of age on T cell generation and TCR diversity. The Journal of Immunology, 174(11), 7446-7452.
 Steinmann, G. G., Klaus, B., & MÜLLER‐HERMELINK, H. K. (1985). The involution of the ageing human thymic epithelium is independent of puberty. Scandinavian journal of immunology, 22(5), 563-575.
 Turke, P. (1995). Microbial parasites versus developing T cells: An evolutionary “arms race” with implications for the timing of thymic involution and HIV pathogenesis. Thymus, 24, 29-40.
 Aronson, M. (1991). Hypothesis: involution of the thymus with aging–programmed and beneficial. Thymus, 18(1), 7-13.
 Dowling, M. R., & Hodgkin, P. D. (2009). Why does the thymus involute? A selection-based hypothesis. Trends in immunology, 30(7), 295-300.
 George, A. J., & Ritter, M. A. (1996). Thymic involution with ageing: obsolescence or good housekeeping?. Immunology today, 17(6), 267-272.