A declining immune system is one of the biggest hurdles we have to overcome as we age.
No matter what longevity interventions you practice,
if your immune system is defunct,
any opportunistic disease that comes along can wipe you out.
In this video, we’ll take a look at possible pathways for regenerating the thymus,
a little-known gland that plays an enormous role in the health of our immune systems.
Today, we’re going to be talking about the thymus…and thymic involution.
Now, I’ve talked about this before, in other videos,
and it you’d like to learn more, I’ve put links to those videos in the description.
Alright, let’s get started.
What the hell is thymic involution? Or for that matter, what is the thymus.
The thymus is a small organ, about the size of your thumb,
and it’s located in the front of the chest, right behind the sternum.
And it’s where T-Cells come from.
In fact, the reason they’re called T-Cells is because it’s in the thymus that they learn how become T-Cells.
And T-Cells are an incredibly important part of your immune system.
It’s the part of your immune system that has a memory,
and that can recognize any pathogen that’s it comes into contact with.
And it’s the part that make vaccines work.
T-Cells are created through a selection process.
It starts with something called a thymocyte.
Thymocytes are a form of stem cell and they’re stem cells that can be turned into T-Cells.
During a part of that process, immature thymocytes are tested to see if they have receptors that a variety of pathogens can bind to.
Only a small percentage pass.
Most thymocytes fail this test, and when they do, they enter apoptosis…programmed cell death.
Those that pass go on to become T-Cells.
And all this happens within the thymus, in a structure called the thymic epithelial space.
Although thymocytes are created within bone marrow, they’re carried by the blood to the thymus,
where they undergo this selection process.
So the thymus is critically important to the immune system.
The health of the thymus dictates the health of the immune system.
But as we age, the thymus begins to shrink.
This is something that happens to almost all vertebrates.
The tissue of the thymic epithelial space begins to shrink and be replaced by adipose tissue.
And this process begins almost as soon as we’re born.
By the time we’re 25, we’ve already lost 30% of our functional thymic tissue.
And we’ve lost half by the time we reach 60.
This whole process is called Thymic Involution,
and with thymic involution comes a decline in the output of mature T-Cells.
Which means a decline in our immune system.
This is why the elderly are at such high risk of catching diseases,
why the diseases are more likely to be severe and end in death,
and why vaccines don’t work as well on the elderly.
So, preventing or reversing thymic involution has been the goal of longevity researchers for a while now.
They’ve been looking at ways to stop thymic involution and to regrow or regenerate thymic tissue.
And they’ve met with some success.
From 2015 to 2017, Dr. Greg Fahy conducted a trial
called the Thymus Regeneration, Immunorestoration, and Insulin Mitigation study.
Or the TRIIM trial.
They took a small group of 10 men,
between the ages of 51 and 65,
and they administered HGH, DHEA and metformin for a year.
After a year, MRI scans confirmed that across the board,
there had been significant regeneration of functional thymic tissue.
The participants also showed signs of immune system rejuvenation.
But that’s not all.
All 10 men were epigenetically tested to determine their biological age,
both before and after the trial.
But instead of being a year older at the end of the trial,
they were, on average, a year and a half younger.
That’s a total reduction in biological age of 2.5 years.
Dr. Fahy has another trial ongoing right now, called the TRIIM-X trial.
It involves a much larger cohort and one that’s more diverse,
including men & women from several different ethnicities.
The goal is to see if the same results can be duplicated in a much larger and more diverse group of people.
So, looking for a way to stop thymic involution and regenerate thymic tissue is not only a worthy pursuit,
it’s a key component to extending human life.
And a new study that came out in October of this year
has revealed that another group of scientists may have discovered a way to regenerate thymic tissue using a very different pathway.
The thymus is an incredibly delicate organ,
and can be damaged quite easily, by cancer treatments, such as radiation and chemotherapy,
by infection and simply by aging.
As is evidenced by the whole process of thymic involution.
But believe it or not, the thymus also has an amazing capacity for regeneration.
And a research team out of the University of Washington in Seattle
is looking into ways to unleash that capacity.
This team, led by Drs. Jarrod Dudakov and Sinead Kinsella,
has discovered that this damage to the thymus is the very thing that might unleash the thymus’ capacity for renewal.
Here’s how it works.
There are two pathways in the thymus for regeneration.
One pathway is triggered by a molecule called IL-22
and the other pathway by a molecule called BMP4.
However, and there’s always a “However”, right?
Well, those pathways get suppressed, and no new thymic tissue is generated.
Remember those thymocytes, those immature T-Cells that I mentioned earlier?
The ones that didn’t make the grade and wound up dying off in droves, by apoptosis.
They discovered that those dead and dying thymocytes acted as a brake to keep IL-22 and BMP4 suppressed.
Turns out that those dying thymocytes are detected by a pathway called the NOD2 pathway.
That detection triggers a signaling molecule called Rac1,
which sends a signal that shuts down the production of both IL-22 and BMP4.
That’s what usually happens.
But when the thymus is damaged, whether from infection or radiation or chemo,
that damage destroys all T-Cells,
both the mature T-Cells and the immature thymocytes.
With the profound depletion of the T-Cells caused by damage,
there’s an absence of apoptotic thymocytes.
So, detection drops and the suppression of IL-22 & BMP4 is attenuated, or lessoned.
As a result, production of IL-22 & BMP4 is increased and the thymus begins to regenerate itself.
So, theoretically at least, all you need to do is to regenerate the thymus is to suppress detection of apoptotic thymocytes.
And the research team believes that this can be done pharmacologically.
They’re now working on a drug that acts as a Rac1 inhibitor,
preventing detection of apoptotic thymocytes and the signaling to shut down the production of IL-22 & BMP4.
They’re also trying to demonstrate that thymic regeneration can boost immune responses in older mice.
The biggest problem is that there are no Rac1 inhibitors available for clinical use,
but the researchers are hopeful.
Molecules that are related to Rac1 are implicated in numerous diseases
and are an active area of investigation by pharmaceutical companies.
So, while regeneration of the thymus pharmacologically is still a ways off,
it’s really starting to look like this is a puzzle that will eventually be solved.
And that wraps up another video.
If you’d like to learn more about thymic involution and Dr. Fahy’s TRIIM study,
check out these videos.
That’s it for me, I’m outta here. Catch ya next time.