The Aging Immune System, Thymic Involution, and Wnt4

As you might recall, one reason that the immune system declines with age relates to its capacity of cell types. An aged immune system is clogged with useless memory cells, leaving few resources for capable cells to fight new threats. The other reason is the decline of the thymus, source of immune cells:

The immune system undergoes dramatic changes with age - the thymus involutes, particularly from puberty, with the gradual loss of newly produced naive T cells resulting in a restricted T cell receptor repertoire, skewed towards memory cells. Coupled with a similar, though less dramatic age-linked decline in bone marrow function, this translates to a reduction in immune responsiveness

But what if we could regenerate the thymus, restoring it to a vigorous production of new immune cells? That could be one way of pushing out the limits, and making the accumulation of memory cells less harmful at any given age. One of the long-time Fight Aging! readers kindly pointed me to a recent article at Scientist Live on this topic:

Successfully combating illness in elderly individuals can potentially add years to a life. At the centre of this struggle lies an immune system that becomes compromised with age, subsequently leaving the body susceptible to diseases younger bodies would normally keep at bay.

Dr. Claude Perreault and a team of Canadian and Finnish scientists has identified a protein able to stimulate the production of T-cells, the white blood cells involved in the recognition and the elimination of infectious agents.


why does the thymus involute early in life so that it leaves older people immunodeficient. For example, thymic atrophy begins as early as one year of age. Progressive thymic involution is responsible for the fact that elderly individuals have very poor thymic function. They produce very little T-Lymphocytes and because of that they are more susceptible to infections, cancer, and autoimmune disease.

We also found that one major characteristic of the thymus found nowhere else in [the] lymphoid organs is the expression of a protein called Wnt4. We hypothesised that Wnt4 had a role in T-Lymphocyte development and that by providing high levels of Wnt4 to hematopoietic progenitor cells we would enhance [production of immune cells]. That is how it began.

We did two series of experiments. In the first set, we induced over-expression of Wnt4 in hematopoietic stem cells and found that compared to mice that received standard cells those that received cells producing high levels of Wnt4 had a bigger thymus and produced 3-4 times more T-Lymphocytes. ... when we knocked out Wnt4 there was thymic atrophy.

Overall, these studies suggest that Wnt4 is necessary for normal T-cell production and that over-expression of Wnt4 is sufficient to improve [production of immune cells]. In the future, we hope to evaluate the best way to give Wnt4 to animals or humans in order to find whether this molecule can be used to treat thymic involution.

An interesting start; I suspect we'll hear more along these lines in the years ahead.


I would hypothesize that the thymus involutes in order to prevent autoimmune diseases.

The more T-cells an immune system cranks out, the more likely it will make a mistake and attack part of the body. We start off with virtually no immune system so we crank out the T-cells. Most of those cells the vast number of mundane microbes and parasites that infest the natural world. Only the handful that get through get labeled diseases. Maintaining that high rate of T-cell production over the entire course of one's life would dramatically raise the possibility of an autoimmune disease while providing relatively little protection against the vast majority of pathogens.

Posted by: Shannon Love at August 27th, 2008 6:21 AM

Shannon, I know this is a pretty late response but I just came across this article. A correction to your hypothesis. The thymus does not involute for prevention of autoimmune diseases. Actually, adults develop more autoimmune diseases because of the involution. The thymus continually educates, negatively selects, and regulates T-cells. It's height of function actually destroys T-cells that have an autoimmune tendency. The ability of the thymus to do this is called "central tolerance." I wish there was a way to prevent the involution but, as of yet, there's not much we know of. The influx of sex hormones at puberty trigger the involution, this we do know. Perhaps, this is my hypothesis, a good diet that keeps hormones in their correct balance (which ends up being great for other issues as well) may keep the thymus functioning longer. Thank you and best wishes to a long, healthy life!

Posted by: Christine Carr at April 12th, 2012 8:38 PM

Christine Carr, I am currently doing some research on the thymus, where did you find your/where can I find more information regarding central-tolerance and the thymic roll in preventing autoimmune disorders? (I also was under the impression involution occurs to help prevent defective naive T-cell production and potential autoimmune factors).

Posted by: Cody Cummings at November 22nd, 2012 1:41 PM

I am a 37 year old woman who just found out by happenstance (unexpected CT scan) that my thymus never involuted. I would love to know why and what this means. I also have Celiac disease which is an auto-immune disease.

Posted by: Hilary Kahrl at January 30th, 2013 12:56 PM
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