Episode 13: TRIM Trial - A Study in Reversing Aging

Welcome to Inside the Cure with Dr. Charles Moak from Allure Medical. Learn what it takes to cure diseases, not just manage their symptoms. Healthcare isn't going to save itself, so let's jump right in.

Today we're going to review a study that was able to reverse aging in human beings. I'm going to go over a few definitions or terms you may or may not have heard before so you can understand the context of this study. So, first off, there's something called the epigenetic clock, and it's a DNA test that is now commonly used to measure the age of our. Of our DNA, the age of our bodies. So it's chronological age, how many years you are, but your DNA may be wearing out prematurely, and you might have an advanced, chronic, advanced epigenic clock, or you might have done things or had genetics that slowed down aging, and you might be younger than your chronological age. And there's a few different DNA age tests out there. They measure something called methylation of the DNA, and it's really based on something that we commonly refer to as a Horvath clock, after Dr. Horvath, who is instrumental in determining this way to measure aging. There's other ways to measure aging as well. Telomere length. So telomeres are little strands on the DNA, and as they get shorter, our lives are shorter, our future is shorter. But that there's things that adjust that that might not, say, measure out over time. So the epigenetic clock right now is probably the best way to measure age. Second thing I want to talk about is the thymus gland. There's a thymus gland. It's a immune gland behind your chest. And it makes the type of T cell that's viable, sorry, necessary for immunity. So we know that one of the factors of aging is decreased resistance to infections, decrease immunity to cancer, decrease immunity to things that age us. And as we get over 60 years old, the thymus gland rapidly deteriorates and rate of disease accelerates. And there's a clear link to decrease immunity and aging. This is why we see more people who have Covid that are older and have other diseases are more likely to succumb to it because they have less immunity. A lot of the research is based on finding immunity boosters. So these are the two things that they were measuring in the Study published by Dr. Fahey A couple years ago. And it's really something that's caught a lot of attention. And they're doing a second study. The first study is called the trim. Trimm. It was really a Thymus gland study to see if they could reverse in what's called immunosenescence or aging, the thymus gland. And they wanted to see whether or not this caused people to become younger, if they restored a thymus gland. And they used three drugs. Now there's another study going on right now called the TRIM X study. It's the second series and you can enroll in that if you want to. So I'll review that a little bit at the end. The first study, they measured the epigenetic age blood test in nine men that were in their 50s to 60s and measured their age. And then they put them on three study medications on various doses. The key drug they were using and testing was a drug called growth hormone. And growth hormone, as you can guess, is a hormone that's responsible for growth and it does other things as well. And it's been used for doctors for anti aging purposes in the past. It's currently illegal by the federal government. It was back in the 90s. It was very popular for wealthy people to go on growth hormone to slow down signs of aging. That's why they were taking it. Whether or not it worked remains to be debated. And the government outlawed it in the 90s. The only drug that's ever been outlawed to use for is called off label use. So doctors are committing crimes if they prescribe growth hormone for the purposes of slowing down aging. So they did what's called an investigational review board, an investigational new drug. So they have permission to use growth hormone, measure its effect on aging for this study. Otherwise you really can't do it in America. And growth hormone has a negative consequence potentially, which is insulin resistance or elevating the blood sugar. That's a known potential side effect for growth hormone. So they also put people on a drug called metformin, which is used for diabetes, and a hormone called dhea. And both these are known to stabilize blood sugar or make body, your body more sensitive to insulin and to sugar. But also metformin by itself is being studied as an anti aging drug. We know that people on metformin who are diabetes, who have diabetes tend to have less age related disease than their matched peers without diabetes, which is a very interesting concept. And this appears to be the only diabetes drug that does this. And there's a study right now called the TAME trial where they're looking to see if taking metformin in people that don't have any diabetes, if it extends their period of healthiness. And that's an ongoing study for I think about six year study people in their 60s and 70s. So they put them on growth hormone injectable four or five days a week, about 0.15 milligrams per kilogram. So it's weight based, and it was men. The women need a higher dose to make it. Simply, they use the same sex also they use the same dosing. And they adjust the metformin and DHEA dosing as well as growth hormone dosing based on responses. The labs they were looking at what's called IGF1, which measures growth hormone responsiveness. And they measured blood sugar and insulin and some other things. And the study was designed to be involved with treatment for six months and then observation points at one year and 18 months. And they ran the study again for about a year and a half between 2015 and 2017. And what they found was that at the end of the study, at the end of the one year where they're only being treated with the growth hormone four or five days a week, metformin and dhea, the men were on average a year and a half younger than their stated age, which made them basically two and a half years younger than the day they started. So they actually de aged by 2 and a half years on average. All men did respond. Additionally, they used multiple different labs to check the genetic clock and they pretty much got the same results. So it wasn't a laboratory thing or laboratory favoring something that might not be reproducible. They used different companies to measure the epigenetic clock. So it's pretty remarkable. And it's led to a lot of interest in the use of growth hormone to slow down aging. Now, the other thing they're looking at was how did it affect the thymus gland, which is this immunogland behind your chest bone? And it actually regenerated. So the immunosenescence is where the thymus gland or other glands that have immunity sort of die out. Senescence means sort of dying out is sort of where a cell no longer is dividing and it just won't die off. It just lays there and is inactive and secretes little cytokines, make other cells inactive. And it really accelerates after about 60 years old. And they were able to before that occurred. These are mostly men in their 50s, get the thymus gland to start regenerating, which would give them theoretically more immunity to cancer and infections, in addition to reversing their age. Now, there's a few problems with the study of translating into that. What can you do now? So first off, growth hormone, for the purpose of Anti aging is illegal. So. So there's a couple uses that are FDA indications for growth hormone and it can be used for that. It's typically used for, originally used for short stature children. Some children are born without much growth hormone production and they don't grow very well. So we put them on growth hormone and they keep them on it into adulthood because they typically have more disease if they go off of it. And there's some other conditions it's used for. In 1990, there was a study by Dr. Rudman, I think it was University of Wisconsin, where he showed that men in their 60s were put on growth hormone after a few months. They seemed to be looking or seeming younger based on their lean mass and their weight and their response to sugar, and had caused a lot of people to start being interested in taking something that would potentially be like the quote, fountain of youth, unquote. So it was being prescribed and the FDA was concerned that there wasn't enough research behind it. So for the first time ever, they took this drug and made it illegal to prescribe it for anything off label. Off label means using a drug for another use, which is done all the time. That's perfectly legal with the exception of growth hormone. So that presents a challenge for this ever becoming a marketable substance because it's, it's something that the FDA's declared, you know, 25 years ago, that they're not going to allow people to try to take something that might slow down aging or reverse aging. So I think one of the plans of the company that ran the study was to see if they can get a separate FDA approval for thymus regeneration, because that's what the aim of the study could they get thymus to regenerate and if you get a new indication, then it could be used for that. Another problem with this study is that they were also using metformin and dhea, which both of those, perhaps those were the drugs that reversed aging. I doubt it, but that's really impossible. Normally when you do study, you'd have some kind of control. They didn't have a control here. You wouldn't really need to control in general. If you say, well, you're two and a half years younger, that's pretty obvious that that doesn't happen in nature. But they didn't see was it which drug was it? Was the combination better than just using, say, metformin and DHEA alone? That's not known. Again, like I said, there's another study looking at the use of metformin on aging. To my knowledge, There are no metformin and epigenetic clock papers published, so we'd have no way of knowing if this was a metformin effect. So there's another study going on with the same group, I think it's called the TrimX T R I M MX and they're doing some additional things such as NAD, which is a compound that's commonly being used for anti aging and some what's called senolytics, which are drugs that kill off cells that are no longer functioning. And they're gonna have some controls in this study to try to see if there's a way that we could replace reverse aging and reverse the effects of aging. And a question would be, I hear this a lot. Well, I don't know if I want to live to like 120 because I'll be all frail and sick for a longer period of time. That's really not the goal of most scientists that are looking at aging. They're trying to expand the period where you're healthy, the health span and what happens. We know from studies on animals, if you make the animal younger, the diseases go away. Okay, so diseases associated with aging go away once you're younger. In the study done that referred to with growth hormone. It wasn't powerful enough to determine if this happened because these men weren't sick and they didn't have enough people in the study and they didn't measure enough things. But in general, the goal of anti aging therapy or reversing age is to make you healthier for a longer period of time so you're still productive and able to have family and friends and enjoy things versus just hanging in there longer, which obviously most of us wouldn't really want. So we're seeing this coming. We're seeing a lot of research and studies being done first in yeast and then in animals, flies, mice and some other larger mammals that more closely resemble humans, such as primates. And they're seeing positive effects on being able to slow down or reverse aging and age related disease. And this is really exciting. There's people that are currently self experimenting and are showing on themselves that they've reversed factors of aging. I've certainly done some of those things and have been able to prove that I could de age certain organs in my body, make them younger. My genetic age, I measured that about two years ago. I measured again just about two weeks ago. I'll see if, if I've slowed down aging or reversed it at all, I won't know. For it takes about a month to get these tests back and the tests for epigenetic clock only cost about $300. So they're not very expensive. The telomere tests which are commonly used in the past decade or so are about 200 bucks. A little cheaper but not as accurate. So I would probably be in favor of doing the epigenetic clock. However, myself I've measured both and we'll see as time goes on. Do these drugs become available. Now the next TRIM study which using growth hormone, metformin, DHE and some other agents, you can sign up for that, you can just google the TRIMX study and there's a thing on their website where you can ask to become a member and they'll help you fill out a questionnaire and there's certain exclusion criteria. One of the concerns they had was we don't know if growth hormone can accelerate cancer so there's a high family risk of cancer. They recommend you don't enter the study. If you have a problem with blood sugar, they're not recommending you enter the study. So there's certain exclusion criteria and they're looking for this to be self funded. The first TRIM study the company paid for the drug. It's very expensive. Growth hormone is very expensive. In this second one they want you to pay for it yourself. I talked to Dr. Fahey and between the testing of the MRIs of the thymus gland and the blood tests and the drug for men is going to be about $18,000 or probably a few thousand dollars more for women because women require more growth hormone to get a igf. One response that's something. If you want to be part of the clinical study you can and it is totally legal inside of a study to take growth hormone or if you have one of the indications for growth hormone deficiency. So stay tuned. I'm going to be talking about other things and studies that are being done to reverse aging. I've done some things myself to reverse markers of aging. I have concerns about my genetic risk of cardiovascular disease. So I did a very aggressive cardiovascular age reversal and I reverse my cardiac age by 16 years and my mother has severe Alzheimer's and I'm concerned about neurocognitive decline. I did do the genetic testing. I'm not at risk for it genetically, but I did reverse my brain age substantially over about a one year period. So we know these things can occur and can we reverse our genetic age? And the answer is possibly. This study is not enough to say definitively it can be done. But the interesting thing about this study was they had the patients on the drug for six months and they actually aged more. I'm sorry, they actually reversed their age more between nine and 18 months. I'm sorry, between nine to 12 months than they did in the first six months. So it's possible, if this does work, you might only have to do it six months every three or four years. So that would be really exciting. Again, we don't know yet. There's nothing definitive on it. There's other pathways to reversing aging, such as blood blocking, what's called gero conversion. There's a pathway that makes our cells turn old. And there's something called senolytics. Those are drugs that clear out cells that are no longer functional and actually contributing substantially to aging. And I'll talk that in future episodes. So thank you very much.

Thanks for listening to Inside the Cure with Dr. Charles Moak. See you next time.