Halting Thymic Involution

The thymus is a thumb-sized organ just above the sternum where our immune cells are trained to recognize self from other. It is fully developed by the time we are 10 years old, but after that it begins gradually to shrink. By age 25, it has already lost 30% of its mass, and by age 60 it is less than half its peak size. There is evidence that this is related to the immune decline that contributes so much to growing mortality risk with age, and that reversing that decline might lead to longer, healthier lives.

 

As we get older, the white blood cells that protect our bodies from cancer and infection become less effective. They make two kinds of mistakes, for which statisticians apply the creative terminology “Type 1” and “Type 2”. Type 1 mistakes are a failure to recognize the invader, and it is the reason that, for example, older people frequently die of influenza and pneumonia, while younger people seldom do. Type 2 mistakes are false positives – inadvertently attacking the body’s good, healthy cells as if they were an invader, with consequences that are even worse for us than Type 1. It is the root cause of auto-immune diseases and inflammation that are hallmarks of old age in mammals.  Decline of the thymus is intimately related to both types of errors.  There is indirect evidence that thymic involution exacerbates other aspects of aging as well, and there is lots of evidence correlating immune decline with mortality, independent of age.

T-cells are a kind of white blood cell that responds to new infections, and then remembers for many years (“memory T-cells”) the disease to which you were exposed, so that if it ever appears again, your immune response is jump-started. The “T” in “T-cell” stands for thymus, and it is in the thymus that these cells are trained to recognize all the 30,000 or so proteins that the body produces internally, and to attack any protein that’s not on its “white list”.

Once an invader is recognized and an immune attack is mounted, the particular cell that successfully identified the invader is rewarded with profuse replication, flooding the bloodstream with copies of itself until the infection is successfully repelled. After that, most of the clones die away, but a few remain circulating in the blood for many years afterward, just in case the same pathogen should appear in the future.

T-cells, then, are either “naive” or “memory” cells. It is the naïve cells – newly manufactured and trained in the thymus – that enable you to launch a defense against new (to you) diseases. The number of naïve cells declines with age, and the decline has been linked directly to shrinking of the thymus gland

Thirty years ago, a research lab in Tokyo tried grafting thymus glands from young mice into old mice. They repeated the operation every few months throughout the the lives of the older mice, and the mice lived half again as long as controls that didn’t receive transplants, despite the periodic trauma of the surgeries. (Of course, the donor mice had to be genetically very close to the host mice, because the immune system is ultra-specific to individual genotype; but that was easy to arrange, because lines of laboratory mice are routinely inbred so that they are genetically homogeneous.) Thymic involution is common to all vertebrates, and it is a good bet that it contributes substantially to aging in most if not all species, including humans.

There is no known benefit to humans or any animal from having a smaller thymus, so thymic involution is a good candidate for a mechanism of programmed aging, an aging clock like those described in this space two weeks ago.

 

What to Do About It

There are many studies with humans and animals reporting that thymic involution can be reversed and immune function restored with growth hormone (GH).  I hasten to add that I don’t recommend growth hormone for other reasons: it can lead to diabetes and cancer. Growth hormone has also been associated with increased mortality when administered to critically ill patients, (even though they were deficient in GH). A friend and colleague of mine experimented on himself in a controlled, medically-supervised trial, and succeeded within one month in regrowing his thymus and increasing immune function, – after which he was wise and knowledgeable enough to discontinue his own treatment (written up here).

Besides GH and thymus transplants, other interventions have measurable but less dramatic benefit for regrowing the thymus. These include thyroxine, interleukin-7 (IL-7) and luteinizing hormone (LH), supplementation with melatonin, arginine or zinc, and castration. (ref).  I realize that some of these interventions may be more appealing than others.

The hormone ghrelin has also been found to stimulate thymus growth in mice. The mechanism seems to be related to GH, since ghrelin binds to a class of receptors called Growth Hormone Secretagogues, stimulating endemic production of GH. Ghrelin also make you hungry, and there was some hope a few years back of manipulating ghrelin levels as a diet aid. This is one more suggestion that the same signals that make the body hungry contribute to life extension from calorie restriction (ref).

Thyroxine actually has other anti-aging properties as well – a topic for another day. LH may be a mild alternative on the castration axis: it tends to suppress production of testosterone. Leuprorelin (trade name “Lupron”) has been prescribed to prostate cancer patients because it cuts off testosterone very effectively, and presumably for that reason it would be a non-surgical substitute for castration.

IL-7 has been studied as therapy for cancer and some other illnesses where increasing immune response is desirable . In mice as in people, IL-7 has been shown to increase T-cell production and to stimulate re-growth of the thymus. Is it safe to use for a general population, not in extremis? The reason we’re not likely to find out soon is that IL-7 is priced like a cancer drug, at $10 million per gram

 

Neglected Opportunities

Research on reversal of thymic regrowth is a backwater of medical science. If this is an opportunity for major gains in life expectancy, then it is a neglected opportunity that has attracted little interest or funding. Based on evolutionary arguments, the general attitude seems to be that if the thymus shrinks over a lifetime, then it must not be much needed; or, conversely, that a Law of Nature assures us that any therapy to maintain its function must necessarily have dangerous side-effects that outweigh the benefits. Wikipedia calls it an “evolutionary mystery”:

Since it is not induced by senescence, many scientists have hypothesized that there may have been evolutionary pressures for the organ to involute…the best time to have a prodigiously functional thymus is prior to birth. In turn, it is well known from Williams’.theory of the evolution of senescence that strong selection for enhanced early function readily accommodates, through antagonistic pleiotropy, deleterious later occurring effects, thus potentially accounting for the especially early demise of the thymus.    (Wikipedia)

But this is ideology, a misplaced faith in general theory over explicit experimental results. Reality in the lab appears to be that

Thymic involution, adrenal involution, and somatic involution seem to provide no obvious benefits in humans that would outweigh the benefits of their elimination once the hazards associated with such issues as insulin-like signaling can be set aside. Fortunately, methods of eliminating or at least blunting thymic, adrenal, and somatic involution or their effects are already known…and will surely be improved in the future. (Fahy, 2010)

I remain hopeful that

An understandin of the causal mechanism of thymic involution could lead to the design of a rational therapy to reverse the loss of thymic tissue, renew thymic function, increase thymic output, and potentially improve immune function in aged individuals. (Aspinall and Andrew, 2000)

 

Much of the material in this article was derived and elaborated from a book chapter by Greg Fahy, who also edited the volume The Future of Aging.  Chapter 15 by Richard Aspinall and Wayne Mitchell in the same book offers more details.

25 thoughts on “Halting Thymic Involution

  1. Proboost Thymic Protein A I have been using it for immune boost whenever I feel a sore throat, etc; works great!!!

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  3. I was curious, your friend Greg Fahy who did the experiment on himself. How long did the changes last for after he stopped taking GH?

    Thanks!

    • It seems like a reasonable question to ask, but I don’t think that I know how to ask it experimentally. Greg’s thymus was contracting. For a year he took GH. The thymus was larger at the end of the year than the beginning. But after that, can we compare the size of the thymus to the size it would have been, when we don’t know what size it would have been.

      Of course, the right way to ask this question is with statistics. Give growth hormone to one group of people and don’t give growth hormone to another. Compare average shrinkage of the thymus over time. Such experiments are the right way to go about things and we learn a lot, but they are very costly and time-consuming.

      Meanwhile, Greg has done us a favor. We have not a proof but a single data point. An intriguing idea, and an impetus to learn more.

      I’m going to see Greg in a couple of weeks, and I’ll ask if there is data for the years leading up to his experiment and the years afterward from which we might learn more. But I’m guessing that data from just one person will be too noisy to draw any conclusions, assuming there are enough measurements before and after to see anything at all.

  4. During the mid to late 70’s, when my mom was dishing up spaghetti squash for dinner and adding wheat germ to everything else we ate, she was also inclined to “tap” her thymus, insisting it helped her immune system. Has this practice been scientifically explored and debunked?

  5. Seems to me that a big thymus would be necessary in a child which is exposed to many new germs; but a smaller thymus would be adequate in adulthood, after the body developed immunity to most childhood diseases.

  6. Supplemental cow colostrum is said to act like growth hormone and regrow the thymus.
    http://www.secrets-of-longevity-in-humans.com/colostrum-benefits.html
    Thymosin Alfa and Beta are hormones that are naturally produced by the thymus gland (and endocrine gland located in the chest). When a healthy baby is born, this gland is about the same size as their heart. By mid adulthood people past 40 rarely have a thymus glad much larger than a pea and by the time they are seniors, there is usually nothing functional left except some fibrotic tissue strands. A functional thymus gland plays a central role in immune health and studies have shown that raw colostrum can actually begin to re-grow this shriveled gland in adults!

        • Haven’t heard back from him yet. Here’s an excerpt from an article on the subject:
          Research has shown that regular consumption of colostrum can help the thymus gland re-grow to its youthful size. Of primary consideration for rebuilding the thymus gland are the numerous immune and growth factors contained in colostrum. They are known to promote healing, slow down cellular breakdown, and accelerate tissue growth. It is these growth factors that may be capable of restoring the thymus gland and actually returning it to youthful function and proportions. Colostrum also contains a hormone called Proline-Rich Polypeptide (PRP), also known as thymulin. It is essential for optimal functioning of the thymus and helps to establish homeostasis, regulating the gland and immune system up or down as needed.

          Learn more: http://www.naturalnews.com/028833_thymus_colostrum.html#ixzz3eTuv7DKd

  7. The primary purpose of nursing a newborn is to populate its gut with species-appropriate microbiota (which successively occurs by stages over the following months with the same dynamics, abstractly, as seen in ecological succession). Given that, there can be but little advantage in consuming the products of other species (strict herbivores in this case) regardless of pollyanna-ish opinions to the contrary.

    The work of healthspan maintenance is in sporadically vigorous exercise, some form of fasting or calories reduction, a limited regimen of supplements and, for the wishful, a few enzymes, Mostly it requires the discomfort of regular and varied physical exertion (and, perhaps, avoiding suppers).

    • Mounthell – I agree with you entirely. I would like to add that colostrum is sold as an especially good source of growth factors. And that is exactly why I would not touch the stuff. It was meant for baby calves not for adult humans.

      Bovine IGF-1 is identical to Human IGF-1. Read the abstract of a 1988 (meaning old news) article at
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1148968/

      Drinking milk increases IGF-1 production in the liver which in turn leads to an increase in the levels present in the blood. It has been linked to cancer. see the well documented article at http://www.notmilk.com/drlarsen.html

      Colostrum is just a more potent form of milk. Be aware that the self experimenters who take colostrum to try to enlarge their thymus may also be increasing their chances of growing cancer.

      Caveat emptor “Let the buyer beware”

  8. My search for a supplement to increase my immune system since contracting an autoimmune disease brought me to this article and i found it to be an interesting read.
    Wondered if anyone has come across a reliable supplement to increase thymus or simply improve immunity ?

  9. it is said that bovine colostrum can rebuild the thymus back to pubescent levels …. according to some, it possesses igf1 the human growth hormone … it aids in rebuilding the biodome and by extension the entire immune system.

  10. Interesting reads : my wife developed auto immune disease and have had her to Mayo clinic with their backing away,as if afraid to tackle the case. I am a maxillofacial surgeon. My reason for researching this on my own. If anyone can give me any help would appreciate your help.

    • Gary, you might look to Dr. David Brownstein. He is family practice, and has large experience with thyroid autoimmune and adrenal autoimmune patients. You can find his books for sale online.

      Jim Beecham, MD (retired pathologist)

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