Can we opt out of Aging?

Mankind has long searched for the fountain of youth. Recent studies indicate that both immunological and global aging processes can be reversed in humans now using repurposed medicines that are known to be safe.  The key is the thymus, the center of your adaptive immune system, which withers starting at puberty but can be fanned back to life even after the age of 60.  It turns out that a side effect of restoring your immune system is the reversal of the most reliable indices of generalized aging. Dr. Greg Fahy says he has a recipe for restoring the thymus, although he has a critic or two.  We discuss all that on this episode.  Veteran broadcast journalists Judy Muller and George Lewis are the hosts.

Transcript

Science Straight Up, Season 5, Episode 8

Dr. Greg Fahy

Can we opt out of Aging?

Podcast hosts: Judy Muller and George Lewis

With:  Mark Kozak, Dr. S. Jay Olshansky

(THEME MUSIC)

(JUDY) From Telluride Science, this is Science straight up.

(GEORGE) And on this episode,

(GREG) Mankind has always wanted to do something about aging. We've always wanted to be able to opt out of aging.

(SONG) “If I had my Way”

(GEORGE) I’m George Lewis.

(JUDY) And I’m Judy Muller. Opting out of aging.  It would be really nice if we could do that, and our speaker this time around, Dr. Greg Fahy, thinks it’s possible.  

(GREG) Can we opt of aging?  I’ve got to conclude it’s no longer out of the question.

(JUDY) Some of what he says is disputed.

(JAY) We probably should avoid language that makes claims that we’re gonna live significantly longer.

 (JUDY) And, we’ll get to that later. 

(GEORGE) Every year, Telluride Science brings together about 14-hundred leading scientists for a series of workshops and meetings where they can discuss and debate their cutting-edge ideas.  They also share those ideas with the community in a series of town talks.  This talk was recorded before a live audience at the new headquarters of Telluride Science, the refurbished Telluride train depot.  

(JUDY) I was off for this one, leaving the moderating chores to George.

GEORGE: I’d like to have a show of hands. How many of you would like to opt out of aging turn back the old odometer on the body, twenty, thirty years? (LAUGHTER). 

Those of you who've had recent rotator cuff surgery didn't have to raise your hands. I should have warned you. In my neck of the woods in Norwood, about 33 miles downriver from here, a group of seniors often gather at the Mesa rose Cafe and Bakery for a coffee klatch. They often talk about how they're aging and the various medical procedures they're going through. One of the matrons there calls it organ recitals. (LAUGHTER) 

And Dr Fahy is going to give us his version of an organ recital tonight. He'll talk about a human gland, the thymus, that runs our immune systems. The thymus starts to poop out as we reach adulthood, and then goes downhill from there, leaving us open to all sorts of disorders that we experience as we get older. Restoring the thymus, Dr Fahy says is the key to reversing aging. He's a California native. Holds a Bachelor of Science degree in Biology from the University of California Irvine, a PhD in pharmacology and cryobiology from the Medical College of Georgia in Augusta. He's Vice President and Chief Scientific Officer at 21st century medicine Incorporated, and has co-founded Intervene Immune, a company developing clinical methods to reverse immune system aging. He's also the 2022-2023 president of the Society for cryobiology and editor in chief of the book The Future of aging, pathways to human life extension. Now let us extend a warm welcome to Dr Fahy.  (APPLAUSE)

(GREG) Thank you, George, and thanks to all of you for coming and being so open minded to come even to a discussion about a topic like this, which most people would just reject out of hand. So it's really a pleasure to be here and to see all of you, and I hope that you will enjoy what you hear. I don't have to sell you on this idea of the desirability of opting out of aging, but you're not alone. 

Mankind has always wanted to do something about aging. We've always wanted to be able to opt out of aging. The topic for tonight is, has science finally caught up to that dream of mankind? Can we actually hope to do something like that in a reasonable time frame? Before we get into the meat of that, I want to give you a little bit of perspective, just to open your minds a little bit to the fact that such things are possible according to nature. So there are seagulls that don't have any apparent aging pattern that we can then we can understand so far, and you've probably heard that there are tortoises and whales that can actually live to 200 years of age or so. The Greenland shark is equally complicated. Has a big brain. It's very real organism. It can live for 400 years swimming around in the ocean. Now the ocean's Quahog is mollusk. It's like a big shellfish, and we don't know how long they can live, but a fisherman dredged went up by accident, and they aged the thing. And it was 507 years old. So we know that very long life spans are possible, even among organisms that are even bigger and equally complex to ourselves. 

Aging starts with the thymus. So we have to discuss what the thymus is, and George did a good job of introducing that to you. The thymus is the master gland of the immune system, And Its job is to process cells that come to it through the bloodstream from the bone marrow, precursor cells that are converted into immune system, competent cells called T cells. So, unfortunately, nature has planned something fairly nasty for us, because this vital organ which we all need to survive begins to die when we go through puberty. So, you’re absolutely fine up to the age of 62, because those T cells, even though you’re not making new ones, they still have the ability to recognize every foreign antigen you might come in contact with. But, between the ages of 62 and 78 you lose 98% of your ability to recognize what wants to kill you, and that leaves you defenseless, and that happens to be the age at which you all start to die of the flu, pneumonia, cancer, all these other things that happens to just be the age range in which the mortality rate overall accelerates. 

So I thought this for a long time, but got really good validation of the importance of the thymus at the end of last year from the New England Journal of Medicine. They did a study of people who had open heart surgery. The thymus, as I showed you, is right in the middle of your chest cavity. So they go right through the middle of that thymus in order to get into your heart to do surgery. So a lot of people think, Oh, the thymus is no big deal. This is only fat anyway. They just throw it away. It's in the way. So they did a retrospective study to say, Okay, people who got open heart surgery, what happened to the people they threw the thymus away versus those who they kept the thymus for? Well, the answer is pretty staggering. Five years later, the people without a thymus had a threefold increase in the risk of being dead. They had a twofold increase in the risk of having cancer. And if you had cancer before, they had almost a fourfold increase in the risk of having that cancer come back. And even worse, if the cancer did come back, you were seven times more likely that it comes back in a very virulent form that they need all kinds of multi modal therapies to deal with so you need your thymus. I think you've all been convinced of that at this point. 

So my buddy and I started a company, and we decided to see if we could regrow the thymus in healthy adults between 50 and 65 years of age, the thymus. The trial is called the TRIM trial, and I'll refer to that acronym for a while, stands for thymus regeneration, immuno restoration and insulin mitigation. I'll explain that in a second. 

It was we actually published the study in 2019 and aging cell and so the way it worked. Says when you're young, you have a lot of a hormone called growth hormone. And we know from animal studies and even from human HIV patient studies that you can regrow your thymus using growth hormone, exogenously supplied. But there's a problem with that. The problem is that when you're young you got all this growth hormone. Everything is fine, of course, but if I give an older person growth hormone, they start looking like a diabetic. It inhibits their insulin sensitivity, so their glucose may go up a little bit, but their insulin goes way up. Unfortunately, this is a cardinal sign of aging. This is what happens to us with aging. So I don't want to try to counteract one kind of aging and cause another kind of aging. So we use growth hormone in combination with two other agents, another hormone that's plentiful in youth called DHEA, and the world's number one anti diabetes drug, Metformin, which has other advantages as well. DHEA is made by your adrenal gland. It's present in very high concentrations when you're young and when you're old, it goes away basically. And so I hypothesize that maybe the reason we have DHEA is to block this side effect of growth hormone. 

So I test it on myself. It works every time. So now we use DHEA and metformin to block the diabetogenic effect of growth hormone. But this turns out to have another advantage, because all three of these agents have anti-aging effects of their own. So using two anti-aging agents to counteract the side effect of another anti-aging agent seemed like a good idea, and it turns out that it was. So did it work? The answer is yes, it did work.

(JUDY) Although Dr. Fahy’s first study had only a limited number of subjects, nine men, his research attracted the attention of UCLA’s Dr. Stephen Horvath, who has developed methods for determining the biological age of humans, using the properties of their DNA, something called methylation.  And what he discovered was pretty amazing.

(GREG) Steve was kind enough to analyze our data using his original DNA methylation aging clock. And he was floored, because as the guru of aging measurement, he's had people send him samples from all over the world, every conceivable thing, and he never saw aging go in reverse. Generally speaking, people just wanted to slow aging down. Most of them didn't succeed. And so aging reversal by these clocks had never been demonstrated in any system, including in animals. And how we have this human clinical samples going in reverse by two and a half years after a year of treatment.

 33%, three out of nine guys in the trial had their hair darkened again as well that we were not expecting that, so we didn't document it very well. But this guy's wife kept saying, Hey, honey, your head is getting darker. What's going on. So we got some before and after photographs. We're able to document it. In his case, still, you know, this is pretty incredible. I mean, is this really possible? Can we I mean, we have to pinch ourselves every once in a while. We can't just accept all this at face value. We need to have some other frame of reference to make us believe our own results.

So it seems that the thymus does more than just give you an immune system. The thymus may be a pacemaker of aging that's involved in the control of how aging unfolds in general, and in that context, it makes more sense that we're actually able to get this global aging reversal effect on top of the immune benefits that we saw. So this is all very well and good, but in science, nothing is true until it's true twice. So you have to be able to show you can do it again. Otherwise, you know, it's just some kind of random occurrence that just happened by happenstance. So, we started a new trial called the trim X trial. Trim X has been divided into different phases, but the first one is trim x A we X stands for an extension of the original trial. The original trial we just had nine guys. The new trial had 26 people in it. Original trial had no women. The new trial has at least six, which is not a lot, but at least it's something.

We can do meaningful aging intervention in humans right now, not in some distant fairy tale land. We can do something really important about aging right now, and the benefits that we are seeing seem to be linked epidemiologically to the likelihood of improved survival, improved cognitive function, and lack of other kinds of problems with aging. And we seem to see real life health benefits, such as increased exercise capacity and that sort of thing, improved cardiovascular fitness indices, and all of those other alternatives or parallel achievements in anti-aging, they're all compatible with this treatment that we've been developing. So you start adding all this stuff up, and it's not going to be your grandfather's aging process anymore. You're looking at a completely different kind of future for us as individuals, and how our lives will be. So, to combine come back to the question raised at the beginning of the talk, can we opt out of aging? I have to conclude it's no longer out of the question. So, thanks for your attention.

(APPLAUSE)

(JUDY) A couple of caveats here.  Dr. Fahy’s studies are still underway and other scientists will have to weigh in on his results.  And, in an article published in the scientific journal Nature Aging, Dr S. Jay Olshansky of the University of Illinois, Chicago said there’s evidence that average maximum life expectancy will top out at about 87. He says that extending life beyond that will be pretty difficult, absent some sort of breakthrough.  

(GEORGE) Dr. Fahy is treating himself as part of the study, something that came up as I questioned him.

(GEORGE from talk) I’m going to ask Greg Fahy a few questions and then we’ll turn it over to the audience for questions. I want a little audience participation here. How old do you think Dr Greg Fahy is?

(AUDIENCE REACTION)

(GEORGE) He is 85 he said. (makes game show buzzer sound)

(GEORGE) Okay, another guess. Sixty-seven.   Fifty. (to Greg) How old are you? Sir?

(GREG) I'm 74.

(AUDIENCE HUBBUB)

(GEORGE) So, there's a long history of self-experimentation…

(GREG)  That's true 

(GEORGE) …in medical science, and you have self-experimented here. Looks like the experiment worked for you. 

(GREG) Well, I'm encouraged. Yes, I was very frustrated because the possibility of doing the sort of things that we're doing was discovered in 1986 a paper came out in a very prestigious, high profile scientific journal showing you could regrow the thymus of rats. And I thought, whoop dee doo. This is it. You know, this is great, and nobody did anything. So five years later, I wrote an article about aging intervention and pointed this out and said, you know, people should do something about this, and nobody did anything about it. So five years went by, and I decided I had to take matters into my own hands. So I regrew my own thymus, and I used DHEA and growth hormone to do that. I fortunately had a physician who is also interested in aging, and let me do those experiments on myself, and I actually published that. So yes, I've been playing around with these kinds of things for a long time.

(GEORGE) So..how long can we live with these techniques?

(GREG)  Well, the only way to tell is to wait for all of us to die, right?

(LAUGHTER)

(GREG)  So we can only guess. We can only guess. At this point, the question you're really asking, I think, at the end of the day, is, is there a biological limit to lifespan? Is there some barrier that we're going to run into that we can identify today? And I don't know of one. I know of people who have claimed that there are barriers, but I don't think their claims are based on anything significant. There are questions that are unanswered, there are things that we may have to deal with in more detail as we go along. But if you can be a shark and live for 400 years, why can't you be a human and live for 400 years? So we will see, we will see we don't really know the answer. I think we can opt out of aging eventually. I think maybe we could even opt out of aging now, but we have a lot to learn. These are early days. In spite of all the data I showed you, there's a lot more that we don't know than what we do know.

(GEORGE) Let me play hard-nosed journalist for a second. Okay, you've heard the expression. If it sounds too good to be true, it probably is. 

(GREG) Yeah. 

(GEORGE) Now, what do you say to skeptics who tell you that?

(GREG) The funny thing is, nobody tells me that.

(GEORGE) Really.

(GREG) Yeah, I’m shocked.

(GEORGE) Actually, there is that researcher in Chicago, Dr. Jay Olshansky, who says we can’t opt out of aging. Here’s what he told the International Longevity Alliance.

(JAY) If folks are coming along claiming that they’re gonna achieve radical life extension, through any of these interventions, I would suggest that this is an untestable scientific hypothesis and We probably should avoid language that makes claims that we’re gonna live significantly longer as a result of something that requires decades to get an answer to.

(GEORGE) When I emailed Dr. Olshansky and asked him about Greg Fahy’s claims, he responded, quote, “Reversal of markers of aging is not the same as reversing aging itself. Many folks in this industry are treating biomarkers — they have no measure of health span or lifespan, so if they're telling you they can change their biomarkers, this may be true. But that can't prove that it'll make you live healthier or longer.  In other words, it’s like going off daylight saving time. You can turn back the clock, but you’re still getting older.

(JUDY) Greg Fahy told our audience in Telluride that he makes a distinction between reversing aging markers and reversing actual aging itself. But he says his test subjects have shown increased strength and vitality, and that, he maintains, is an indication of aging reversal.

(GREG)  I try, at least to be careful, to always say that we're reversing epigenetic aging, and if I've failed to do that tonight, then blame me. But I personally think that it really is aging that we're reversing, but in order to prove it, we would need more data. We'd have to have deeper information about each organ system in your body and how that's working, but all of the data is consistent with the reality that we're reversing global aging.

(GEORGE) Dr Fahy’s combination of human growth hormone and anti-diabetes medications also provoked a warning from Dr. Olshansky in Chicago.  He wrote---quote— Human growth hormone should never be used for an aging intervention — not only is it illegal to do so, it is also linked to cancer.  Not so, says Dr. Fahy. He maintains using growth hormone is perfectly legal when given in a formally recognized human clinical trial, and that what he’s doing has approval from the Food and Drug Administration.  He also gave us a list of studies that show no increased risk of cancer from using growth hormone.

(JUDY) Back at the Depot in Telluride, our audience was fascinated by Dr. Fahy’s talk.

(GEORGE) I'm going to turn it over to the audience for questions. Mark, are you going to be the microphone holder? Mark Kozak will bring you the mic. Wait for the mic because we're trying to turn this into a podcast, and we want to, we want to pick up your questions clearly. 

(MARK) I think I’ve got something I want to ask. 

(GEORGE) Okay, Mark has a question. 

(MARK) t's got to be some benefit to carrying the mic around. Why do you think your body ages along the time frame that it does currently? 

(GREG) Well, if you if you compare aging across different organisms, it's kind of like a rubber band. You can stretch it to any length that you want, but the life history events kind of unfold in the same way. So the time you spend after puberty relates to the amount of time you spend during puberty, and that relates to how big you are. So if you are an organism like a human or a whale or an elephant, it takes longer to go through the maturational phases, and so that just sort of stretches out the rest of the lifespan accordingly. So I think that's the kind of thing. So as as life was evolving on the planet and finding different niches for different species, some of the species had an advantage of being bigger than the other species, and we have happened to have certain advantages as well. So we achieved this sort of body size, and we ended up with the lifespans that we have.

(QUESTION FROM AUDIENCE) Have you talked to the FDA about what you would need to do to be able to start treating patients, what, what level of evidence you'd need to produce? 

(GREG) Yeah, well, we, we've talked to the FDA in a general way. They know what we're doing. They've approved all of these trials. So this combination of three agents is considered a new drug entity by the by the FDA. But they're, they're not worried about it, because everything is vanilla, you know. GH has been around in human adults since 1996 the D HEA is over the counter, you know. And metformin is the most popular drug, you know, on the planet for diabetes. So they know about it. So, so, so the answer to your question is no, but that's definitely something that we want to do. 

(QUESTION FROM AUDIENCE) Following up on that, I’m wondering if you’ve had any interesting side effects?

(GREG) Uh..well, DHEA can increase libido, especially in men.  (laughter) 

(GEORGE) How are the sex lives of your test subjects? (laughter) That’s the question we all want to know.

(GREG) Well, it's it's interesting. So we had a we had a film crew come and interview some of our volunteers earlier this year, and then they went through the whole thing about how they were doing and everything. But the woman just insisted on telling the the film crew how great her sex life had become when she was on the trial. So I, you know, I take that as a positive side effect. 

There are some side effects, though they affect about 30% of the men and the women. Equally, I'd say the worst side effect is arthralgias. So one of the interesting things that growth hormone does, that I'm not sure anything else does, is it tries to grow your cartilage. As we get older, we develop arthritis, because we lose cartilage cells, and then that doesn't build up the cartilage matrix, and you get bone on bone, and it's really but, but, but growth hormone actually reverses that process. So it multiplies the cartilage cells. They build up the matrix, and that's very well and good, except for one thing, which is that when you go through puberty, the ends of your bones change their structure. The epiphysees close, and that means the bone cannot grow anymore. But growth hormone doesn't know that it's trying to grow you. That's what it does. And so it builds up the cartilage, and you sometimes get some joint pain. It can also build up the muscles in your arm and the tendons, and you can get what people call carpal tunnel syndrome. But almost everybody in the trial who experiences that is so happy with everything else that's going on that they say, Screw it. I'm just going to suffer. So I think, I think it's rare. It's very rare when that problem becomes limiting. And I there's certain tricks that I can do to reduce those symptoms as well, and people that need it,

(QUESTION FROM AUDIENCE) So if one wanted to test the health of their thymus today, what would you do, and then are there, or have you studied any natural ways to increase the health of your thymus versus using a growth hormone?

(GREG) So the answer the first question is pretty discouraging. You just cannot go down to your local blood draw place and order, a test for naive T cells for the most part, or for thymic hormones. The best way to see how your thymus was doing would be to measure thymic

 hormone levels. We try to do that ourselves, but we there's no not only can you not order from your local blood draw place, but all the kits that have been marketed for that, they don't really work. So we're developing those assays in our own lab, because we need them for ourselves. But when we develop all of that for ourselves, then we will also create that as a product, so that we have some income to pay the bills, so that we can keep all of this stuff going, and then you'll be able to answer that question. 

(GEORGE) Well, we want to thank Dr Greg Fahy, let's give him a big hand (APPLAUSE)

(MUSIC)  “If I had my Way”

(JUDY) That’s it for this edition of “Science Straight Up.”  We want to thank our sponsor, Alpine Bank and thanks to our audio engineers, Colin Casanova and Vicki Phelps. Mark Kozak is Executive Director of Telluride Science and Cindy Fusting is Managing Director.

(GEORGE) Annie Carlson runs donor relations and Sara Friedberg is lodging and operations manager. For more information, to hear all our podcasts, and if you want to donate to the cause, go to telluride science-dot-o.r.g.  And thank you to the Library of Congress for that version of ”If I had my Way” recorded a one-hundred ten years ago.  

(JUDY) We should live so long.  I’m Judy Muller.

(GEORGE) And, I’m George Lewis, inviting you to join us next time on Science Straight Up.