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These Molecules Reversed Aging by... YEARS! [TRIIM Study Explained - Study 216]

Physionic13:57

Transcription

There's this study that was published back in 2019 that shows definitive signs of reversing aging. Hopefully, if you've been part of a Physionic for a while, you know that I'm pretty cautious about my statements and try not to say things that don't have substantial proof behind them. But for once, there's published proof. Beyond that, the results looked so promising that the study is being redone with more people in a phase two clinical trial.

So, considering you don't care about getting younger, we'll just end the video here, and I'm sorry to have wasted your time. Oh, you do have like a passing interest? Oh, okay, well, I guess we can spend a few minutes touching on the study results then, but feel free to leave if you get bored. I have a tendency to talk people's ear off when it comes to science.

This study was performed at the Stanford Medical School and involved 10 healthy men between the ages of 50 and 65 years. The researchers wanted to know if they gave these slightly older men a cocktail of molecules, if it would have effects in a few measures of overall health. More specifically, they were interested in immune health and their epigenetic aging. We'll return to that last piece in just a little bit.

This study is called the TRIM study and was introduced to me by a Physionic Insider who wanted my opinion on it. I had a chance to parse through the data for one of our live sessions, and while I found certain aspects underwhelming, I did find other aspects pretty fascinating, especially in relation to aging.

So, what did the researchers actually show? The study ran for roughly 18 months. I say roughly because certain endpoints were only measured up to 12 months. Anyway, the researchers measured the inflammatory molecule C-reactive protein, which is secreted from the liver, and according to this data, showed CRP levels drop at the 9 and 12 months of this anti-aging cocktail. These are pretty profound changes, with around a 30 to 40 percent drop at the 12-month mark.

Additionally, kidney function, measured as glomerular filtration rate, improved starting at the nine-month mark. Oh, and by the way, I'm just going to shoot it straight here: there's a really cool coincidence that happens at the nine-month mark. You probably can't see it yet, but once we get further along in this, you'll have a similar "aha" moment like I did. You'll see what I mean; don't worry.

So, the researchers looked at a few other measures like blood insulin and blood glucose, and neither of those two changed. But then again, the researchers were more interested in immune health anyway. So, how did they investigate that? Well, around the age of 60 to 65, people experience an interesting sign of aging that many people actually aren't aware of.

So, it isn't as obvious as a creaky back or exploding knees, but it happens in your chest. And no, I'm not talking about a heart attack; that's pretty obvious in its own right. We're talking about thymic involution. You have an organ that's planted smack dab in the middle of your upper chest, and that organ is responsible for accepting immature immune cells that originate from your bone marrow.

These immature immune cells are then matured and go through a selection process to make sure that they don't become cancerous and auto-reactive, meaning that they attack your cells instead of pathogens. Anyway, that's really beside the point. The point is the thymus is the training facility of your T cells, a critical component of the adaptive immune system.

So, as we age, our thymus is filled in with more and more fat tissue and less thymic tissue. It goes from a fully functioning organ until it's completely shut down due to its envelopment and encasement with fat cells at the age of 60 to 65. A logical question from here would be, "Okay, well, how do we stop this from happening then?" Well, that's where we can return to this study because the cocktail given to these individuals was designed to reverse this involution, and that's why they recruited people who were in their 50s and 60s specifically.

Okay, so this is an image of the thymus of one of the participants. The white outline means the more gray that you see within the line, the more fat tissue is taking over the thymus. So, worse thymic involution. Then, if we add the second image of the same participant, we can see dark splotches; that is fat-free mass, most likely thymic tissue regeneration.

We can see that further evidenced here. I realize that this looks pretty hectic, but each line represents one participant. So, they're not showing the average; they're showing the individual results. If you'll notice, most people experienced an increase in the thymic fat-free fraction, abbreviated as TFFF, on the vertical axis, starting at about five months of intervention and continuing to climb to nine months.

That said, there are also two participants at the bottom that do not experience any change. So, the intervention helps about 80 percent of participants, but not all. Still, clear evidence where at least reducing the thymus fat mass.

Okay, but how does that actually affect the immune cells? So, we've potentially saved their house, their training facility, but what about the immune profile itself? Your body is filled with different types of immune cells. I imagine that this isn't exactly news to you. We have two major parties, like the Democratic and Republican parties, but these parties actually work together towards a common goal to serve you.

One party, the innate immune system, is filled with cells that scavenge like patrol officers. The second party, the adaptive immune system, is filled with cells that lie largely dormant until activated to attack a particular pathogen. Anyway, monocytes are immune cells from the former party, the innate system. These cells circulate throughout your bloodstream and can invade into tissues if they need to.

Monocytes can become pro-inflammatory, and one of the chief markers of that pro-inflammatory state is the expression of a protein called CD38 that is expressed on the surface of the cell membrane of the monocytes. So, the more CD38 positive monocytes around, the greater the inflammatory state—or that's the general idea. I would argue there may be some more nuance here, but let's stick with that for the time being.

If we look at measures of CD38 positive monocytes, we see a significant drop from month zero, so that's baseline, all the way to month 12 and beyond. The researchers also looked at some other measures of immunity, like the actual T cells that come from the thymus, but the data is underwhelming and, in my estimation, a bit over-interpreted.

Now, while I would normally still tell you about it, it would still require a lot of off-track explanation for me to ultimately shrug my shoulders and say, "Nah, not good enough." So instead, let's look at the aging data. Have you ever asked yourself, "How do I measure if I'm aging better or am I reversing aging?" I mean, we focus so much on age reversal, yet how many metrics do we actually have to quantify it?

I suppose for the first one, "Am I aging better?" you could just use measures like clinical outcomes, like blood sugar, insulin, testosterone, estrogen, and so on. But how do you measure reversing aging? If your blood sugar is normal, it isn't going to become more normal. So, what gives?

Well, let me introduce you to the epigenetic clocks. Epigenetic clocks are based on epigenetics. We good here? Clear? Okay, I'm kidding. So, epigenetics are simply tags that are applied to your base genome. Your cells have thousands of genes that make up your genome, and those genes are made of DNA molecules. Sitting on and around those DNA molecules are tags like methylation.

These tags encourage or discourage the reading or expression of the gene that the tags are associated with. So, as we age, our epigenetic tags change across our genome. We can track those changes across hundreds and thousands of people, creating a database relating a certain epigenetic profile to a set age. Fascinatingly, this works so well that the relationship is incredibly strong.

So, a researcher can look at a set of genes—let's say Gene A, Gene B, and Gene C—and see what tags the cell has applied to those genes and then refer to the database and determine the age of that person. Pretty cool, isn't it? Well, there are a number of these epigenetic clocks, and the researchers point out the changes across four of them. But let's focus on the average seen here.

The vertical axis is the epigenetic age versus chronological age. So, if you see it go into the negatives, that means that the epigenetic age is indicating a younger biological age compared to how old the participants actually are. Clearly, we see over time of intervention, these individuals experience significant changes in epigenetic age.

However, what isn't shown in this data is something that may give you that "aha" moment that I mentioned earlier. Remember how these individuals saw significant improvements in the C-reactive protein and glomerular filtration rates? That's the kidney function at the nine-month mark. Well, their epigenetic age changed the most dramatically in the final three months of the intervention, specifically from month 9 to 12. They experienced a six-and-a-half-year reversal of age. How freaking cool is that?

Now, that's of course an association, but that's a pretty coincidental one if you ask me. Oh yeah, people who experienced a six-and-a-half-year reversal of epigenetic age that correlates strongly with biological age also experience improvements in several indices of clinical health at the exact same moment. I mean, come on, you can't not make that connection.

Okay, there's a lot here. However, I would really like to see this study redone with more outcomes of interest because although there's certainly some gold here, I still want to see more. And with that, I bid you adieu; it's been a pleasure.

Oh wait, you wouldn't want to know what the researchers actually gave these people, would you? I didn't think this would be of interest to you, but okay, I mean, if you insist, here's the stack:

1. 0.015 milligrams per kilogram of human growth hormone

2. 50 milligrams of DHEA

3. 500 milligrams of Metformin

4. 3,000 IU vitamin D

5. 50 milligrams of zinc

And I can imagine this might raise your concern on your end, especially with HGH, because it might promote cancer. Well, a few metrics of cancer, specifically prostate cancer, were measured, and they were found to be improved, actually. So, markers like free total and risk factor PSA.

However, in measures of liver enzymes, there was a slight increase in serum alkaline phosphatase, which is pretty puzzling. If you have any thoughts, then please, please share them. Other liver enzymes, however, did remain normal and didn't budge.

And when is the next study looking to offer much more information on this topic supposed to happen? Remember, it's in phase two clinical trials, so it's already underway. The expected end date is the end of 2024, and you can bet your rear end that I'll be covering it for you once the data is collected and published. Until then, however, you might be interested in some of my other anti-aging content or else something else of mine.

Well, anyway, I'll speak with you then. Thanks for watching. [Music] Thank you.