Stem cells hold great promise in the field of longevity, potentially restoring function to tissues throughout the body. Scientists are also actively studying stem cells as emerging therapies for diseases and disorders. However, for those considering this option outside of a clinician’s care, it’s “not ready for prime time,” said Leonard Zon, M.D., Grousbeck Professor of Pediatric Medicine at Harvard Medical School. He joined Helen M. Blau, Ph.D., Stanford University’s Donald E. and Delia B. Baxter Foundation Professor, during the DOC 2025 session, “Aging, Stem Cells, and Rejuvenation,” as they two spoke with Christine Aylward, founder of Magnetic Ventures, about their own stem cell research.
Blau and Zon are leading the way in stem cell research and its prospective clinical use. Blau’s work on muscle stem cells has shown potential in rejuvenating aging muscle, while Zon’s research focuses on eliminating mutant blood stem cells that can lead to inflammatory responses in the body.
Because of their expertise, Aylward asked the two about common misconceptions around stem cell therapies. Blau noted that while stem cells “have tremendous potential, she worries about “rogue clinics.” She mentioned hearing of people getting fat stem cells injected into their knees, even though the approach doesn’t appear to be effective.
“Nothing bad has happened, but nothing good either,” she said.
Zon further added that people should ask questions of anyone offering to inject stem cells into them, including where the material was sourced and how it’s produced. While he “doesn’t have any issue if somebody wants to do this,” he cautions people to be fully informed and “be careful what you’re putting in your body.”
You can hear more from both Dr. Zon and Dr. Blau from their DOC 2025 session in our video, or read our lightly edited transcript below.
TRANSCRIPT
Christine Aylward
So we sit here with two pioneers in stem cell research from opposite coasts. I’m delighted to be here to moderate and to introduce them. So we’ll start with Helen. Helen Blau is the head of the Baxter Stem Cell Lab at Stanford. She holds 20 patents. She is a member of the National Academy of Medicine, the National Academy of Science.
She’s won multiple NIH awards. I was trying to count them, but I couldn’t quite count them all. And she recently won the National Medal of Science from, President Biden in January. So it’s a pleasure to have you here. And, Helen, I think you’re the first to give us a presentation.
Dr. Helen Blau
So it’s a pleasure to talk to you today about aging, stem cells and rejuvenation. First, disclosure, I’m a co-founder of two rejuvenation companies. And another disclosure, I’m an author of a book on stem cells to amuse children and to educate their parents about what stem cells can do. Stem cells to the rescue. So we’re all living longer.
Both men and women are living longer. But this increased life span is not associated with an increased quality of life. It’s more years with chronic diseases. And the goal of our work is to increase healthspan, or quality of life. And we are focused on muscle primarily because muscle is central to everything you do in life, whether you’re a dancer with the ballet or your road dance thinker using your diaphragm muscle.
If you’re Stephen Curry of the Golden State Warriors, you’re using every muscle in your body to shoot those three pointers. But as we age, our muscles become weaker and humans lose 10% of their muscle mass per decade, after the age of 50. And by age 60, 10% of people have what’s known as sarcopenia or debilitating loss of muscle strength. And by 80, it’s 30%. Sarcopenia has severe consequences. Increase frailty. Makes it difficult to perform tasks of daily living, like walking across the floor. And there is an association with increased falls and, that leads to dependency, institutionalization and morbidity. So what can we do about that? We focused on muscle stem cells. These are cells that lie along your muscle fibers and are dedicated to repairing and building your muscle.
They’re poised to spring into action when there’s injury. Divide and fuze into the muscle fiber and refuel it. So we’ve been interested in finding factors that could enhance the function of the stem cells. And we found prostaglandin E2. It’s a metabolite natural metabolite part of the body’s natural healing mechanism. And when there’s an injury there’s a wave of inflammation. And prostaglandin E2 is part of that wave. Notably, the synthesis of prostaglandin E2 is inhibited by drugs like ibuprofen, non-steroidal anti-inflammatory agents. And you’ll see why that’s important. So we wanted to know how important this pathway is. We created mouse models in which we created the receptor on the stem cells or gave a mouse after injury and said like ibuprofen.
As you can see, if you block this signaling pathway, you lose strength. The mice were less strong because the stem cells were unable to divide and meet the needs to repair the injury. In the absence of this signaling pathway. So it is absolutely essential to repairing muscle.
This was picked up by The New York Times. Bring on the exercise. Hold the painkillers. No pain, no gain. And you should know that when you run a marathon or workout in the gym, you are creating little injuries. And that stimulates your stem cells to build your muscle. That’s a good thing. That’s how you build your muscles.
However, you should resist if you feel somewhat achy after running and working out. Because if you take a ibuprofen often, you’re negating the good you did. So we wondered what happens with aging. And like many good things. Prostaglandin E2 goes down with aging, and this turns out to be due to an increase in expression of what we’ve called a gerozyme and aging associated enzyme that degrades the prostaglandin E2.
We discovered a small molecule drug that can inhibit the function of that gerozyme And as a result, if we treat aged mice for one month, with this drug daily, we find there’s a considerable increase in muscle mass, muscle strength, and in endurance. Time to exhaustion. Running on a treadmill. This is due primarily, as you’ve heard from Melissa, about mitochondria. There’s a mitochondrial reconstruction from distorted, vacuous mitochondria now become condensed and useful. There’s a restructuring and remodeling of the tissue. And it’s much we’re able to produce energy and contract and function. What about humans?
As you probably know, older people fail to build muscle in response to training. So when people perform resistance training, for instance, as shown here for young and old for six weeks performing, resistance training, the young will increase their muscle strength by 20%, whereas the age people doing the same amount of exercise increase only 5% anabolic resistance. It’s called an inability of the muscle to respond to this exercise. Unfair. But we discovered that with aged mice, we have yet to translate this to humans. That with aged mice, if they exercise and we give them our inhibitor of the time, they increase 65% of their strength within two weeks. So if this translates to people, it could be quite significant. Another use for this would be in conjunction with GLP-1 drugs.
As you know there’s a lot of weight loss with these drugs and it’s often beneficial. But one of the things that also decreases is muscle. One third of that weight loss is muscle. And what is needed now because you can end up frail, are ways to build that muscle. In conjunction with the GLP one drugs. We went on to study what, the signature of sarcopenia.
What distinguishes healthy, aged and age matched frail, people. And one of the most significant differences is our enzyme. So this suggests that this is a biomarker that could be used. We haven’t proven it’s a biomarker. It’s a hallmark of human sarcopenia that could be used to track people who have sarcopenia or at risk for sarcopenia. And it could be useful in clinical trials of this drug.
So the take home message is that we found that prostaglandin E2 is part of the body’s natural healing mechanism. It’s essential to muscle stem cell function. It’s also essential to muscle fiber function and neuromuscular connections. And we identified a gerozyme 15KDA that degrades the PGE2 and is a hallmark of human muscle wasting. And we’ve discovered that if you inactivate that gerozyme with a drug, you can rejuvenate aged muscles and increase strength.
I want to end with, an animation I created with the team in Amsterdam. As we age, our muscles become weaker. Our muscles, stem cells that are essential for building must, throughout life, try to divide, but often die. Our mitochondrial function is diminished and contractual function is lessened in a downward spiral that leads to muscle atrophy and inhibition of quality of life. But we discovered that young muscle, when injured, releases the metabolite PGE2, which binds to the receptors on the stem cells, inducing them to divide and replenish and restore the muscle. But with aging, the gel design is synthesized, and that degrades the PGE2 so that it no longer can perform these beneficial functions. Mitochondrial function is diminished, contractual function is lessened.
But we discovered a small molecule drug that binds tightly and specifically to the gerozyme and inactivates it. And as a result, PGE2 is increased and that leads to an increase in mitochondrial function and energy stores. Stem cell function and repair of the fibers and a remodeling of aging muscle tissue. So that now resembles that of young. Should this translate to people? It could have a fantastically beneficial effect on those suffering from muscle wasting due to disuse, disease, or aging. There’s the dream.
Alyward
Thank you. Helen. I feel like this talk could have been called muscle loss or aging bodies and muscle loss, because men will also be speaking about that as well. So I’m pleased to introduce, Doctor Len Zon. He is the head of stem cell and regenerative medicine at Boston Children’s Hospital and, Harvard Medical School. He’s known for his work in zebrafish, also a member of the National Academy of Science, and he is a serial entrepreneur as well. He’s founded five companies. He’s in the process of founding his sixth company, which we’ll hear a little bit about. And he’s a phenomenal, trumpet player.
Dr. Leonard Zon
Thank you, thank you. Super great to be here, Jordan. It’s an amazing conference. Meet incredible people. So I’m going to pick up where Helen, left off and, I talked about this a little bit last year. So there’s a growth factor in your body called myostatin. And myostatin is a negative regulator of muscle. So if you look at these animals and the human on the left, they are mutated in myostatin. And the cow there that you see is often called the Schwarzenegger cow because it is bulked up unbelievably. So. Those are carrying mutations. But my company, Scholar Rock, actually made an antibody, called apitegromab And this is, binding to myostatin and inhibits inhibits its activity. And, this, has been tested in a number of humans and it’s been quite remarkable.
The first is, there are children who have spinal muscular atrophy. This is a devastating disease. Many of these kids cannot walk or do anything. And, we, gave them our drug and, and improvement scale. They went up 1.8, points, but 30% of those patients, developed significant strength greater than three points. We had children who couldn’t walk. And then with our drug, they could walk. And I have to say, for me, as a physician scientist, that was one of the most amazing thing. And actually meeting the patients, afterwards, it’s quite, quite amazing. Now, since last year, we actually, did a trial, giving turns up beside the Lilly drug for weight loss.
As Helen highlighted, there’s a tremendous loss of muscle. And, many of you who are on, the Lilly drug or, or in the Novo drug, have protein shakes and take a lot of things to try to keep up the proteins for the muscle. Well, if we give, at plus tears episode, you prevent the loss of muscle, from, the GLP agonist.
Now, if you think about all the uses that this drug could actually have, and, and, the safety was incredible. There was really very, very little problems with it. So, I think this could end up being a longevity drug and, you know, taking GLP using your natural body’s systems to weight loss and then adding in an anti-myostatin antibody to prevent the muscle loss makes a lot of sense.
These are some things over the next year that might come to bear. Now we’re all here to talk about longevity and aging. And if you were to ask me what what is aging? Ten years ago, I would say it’s epigenetic. Epigenetic means you don’t know what the cause of it is. Okay. But a few friends of mine actually sequence the blood of old people. The surprise was there were mutations in blood stem cells in old people. There were particularly three genes that were mutated. All three of these gene genes are epigenetic regulators. So, this is incredibly common. If you see on the graph there, 13% of all 70 year olds have mutated stem cells. This is associated with, inflammation.
The mutant stem cells make mutant white blood cells that pump out inflammatory cytokines. The same ones that you were seeing, were activated by stress. But these are genetically programed to be very stressful. So you end up getting strokes, heart attacks. And, even if you have a stage one lung cancer and you have clonal hematopoiesis, you end up getting more tumors as a result. They even found mutated clones of stem cells in the tumors. So, we think that this is a large part of aging and a large part of heart attacks in the, in the world. And actually, we’ve started a chip clinic at Dana-Farber, clonal hematopoiesis of indeterminate potential. And we have were overrun, overrun with patients, young patients who have heart attacks, who end up having heart attacks because they have mutant stem cells.
What I’ve been trying to do is to look at how to get rid of the mutant stem cells. So hope this movie plays and we guess it won’t. Could you play that movie for me if possible? So what we found is that, a particular white blood cell macrophages, actually, kill stem cells. And, more often the macrophage comes in and it takes a bite of a stem cell. Then, once it takes the bite and removes a little material, 45 minutes later, the stem cell will actually divide. There’s this code of, quality assurance of your stem cells by these white blood cells. We’ve been able to actually, crack the code.What happens is, on the bottom, if you have a high oxidant stress in your stem cells, those stem cells are going to be doomed.
On the top, you see that this grooming behavior is driven by a don’t eat me signal. And, we think now using this code, we can teach the white blood cells to eat the mutant clones of stem cells and then help in the aging and longevity process. And this is something that I’m taking to a new company, called Camino.
Lastly, I just want to finish with what most of the questions I’ve gotten in this meeting is about is, a lot of people are getting stem cell therapy. Jordan and I have a little clinic on stem cells, and, watching people have some results, but also watching people have a lot of toxicity. So you might, have gotten mesenchymal stem cells. This is very, very, very common. And then more frequently, over the past 6 to 8 months, exosomes. So first of all, if you’re going to get these therapies, you might want to talk to Jordan or maybe, we’ve had a number of disasters happen. And my message is you should know if you’re going to get stem cell therapy, what the stem cells are that are being put into your body. Some of these are offshore stem cells. They’re infected. It’s bad. And so we really need to watch out here. Now with exosome terms the literature is really not that great for this. About a lot of people take them and they contain all the things on this slide. Nucleic acids proteins and lipids. And we’ve recently found that stem cells actually secrete exosomes, blood stem cells in particular.
These macrophages that the white blood cells I was talking about get activated by these exosomes. So now for the first time, we’re studying these academically and seeing what’s in the exosomes, how do they, perturb the immune system. And so maybe we’ll get to an answer. But again, if you’re thinking about exosome therapy, please talk to Jordan or me. We’re very happy to help you. So that was my message for today and happy to take questions. Thank you. Okay.
Alyward
Thank you. Lon.I just have a few questions and then we’ll introduce it to the audience. So when you think about stem cells, we no longer at least with your therapy that you’re developing right now, have to remove them from the body and inject them back in.
Dr. Blau
That’s right. So often when you think about stem cell therapies, it’s about removing cells and putting them back in. And inherent in that is a lot of cost and also a chance for infection. What we’ve done is something different. Our drug, stimulates the stem cells that are present in your body and enhances their function. The drug itself induces this, metabolite that then activates the stem cells.
We’re taking advantage of the stem cells you have and rejuvenating their function and enhancing it. So we characterized that they’re really rejuvenated. I think that’s a different angle targeting the stem cells in your body with the drug.
Alyward
When you think about other tissue types beyond muscle, do you think there’s application for other tissue types? Bone, cartilage?
Dr. Blau
We’re very interested. This jersey is not just expressed in muscle. That’s been our primary focus. But it’s also expressed in a number of other tissues. So we’re interested in whether we could develop rejuvenation strategies for other tissues as well, such as cartilage such as the heart, and other tissues where we see this. That’s a very active area of research in our lab, to see how broad this kind of a therapy could be.
Alyward
This is a question for both Helen and Lynn. When we think about we all know about muscle loss. We can see it as we get older. When you introduce GLP-1s, which we’ve all heard about the benefits of GLP-1s, and I can bet that most people might be on a GLP-1 or definitely know people on GLP-1. That increases muscle loss. Two questions. What do we do in the interim before your drugs make it to the market to improve muscle loss? Is it through supplements. Is it should every building be taken creatine? One, how far away do you think you are from being to market? And then two how do you think about what we do in the interim?
Dr. Blau
I think it’s really important to keep exercising and keep using your muscles. You know, move it or lose it. And yeah, I think you really need to do that in order to maintain your muscle. Eventually. This kind of drug, I think will give a boost. And I expect, for instance, someone who, breaks a hip and is prone for a while, they lose their muscles very quickly. If they’re older, it’s hard to get back. Same with Covid and even young people when they break an arm, it takes a while. So if we could this drug could give a boost, could stimulate the muscles and make them stronger. And one of the things I like about our drug is very much directed towards aging, because the time increases with aging. When in aging, you really actually don’t want bulked up muscles because your bones are also weaker. Our drug is enhancing quality of the muscle, the contraction force relative to total muscle. Yeah.
Dr. Zon
I would just add, you know, you definitely need to keep your protein high. If you’re other GLP agonist and, so a lot of people have protein shakes, other supplements are totally fair. You really want to make sure you maintain your muscle because there’s an entire the muscle is not only important for strength, but it’s an important metabolic organ, too. It really helps. And then, for the Scholar Rock drug, it was supposed to be approved two weeks ago. But we had a manufacturing issue with, Catalent. So, we’re on a little bit of a hold until we get it approved, but eventually it will likely get approved.
Alyward
They received a CRL, which is a complete response letter, which basically kind of puts you back nine months to a year for the FDA to go in and look at your manufacturing facilities and then. Can I ask a question about Scholar Rock? Because I think that, as a doctor, you would like to make the most impact with patients, and you are kind of have these two different areas. One is more of a rare disease, much smaller market. Yeah. One is a much larger market. Yeah. When you think about longevity and GLP-1s.
Dr. Zon
It’s a really good question. If you think about it, we treated these children who have this rare genetic disease. That was the initial, trial. We treated 180 of those, children. And, so the drug will likely be approved based on the rare disease indication. But, you know, then we did this trial to have the GLP agonist plus our, plus this drug. It’s possible through doing a phase three trial and, that ultimately this could get used as a, and to be approved, to help prevent the weight loss from, GLP agonist. But it’s also possible that people will just take it because it would be approved for them. So they although it would be costly, more costly than you’d want for one of those drugs.
Alyward
One final question and then we’ll open it up because I see three people standing over there already. What do you think is the biggest misperception about stem cell therapy?
Dr. Zon
I think that there’s an overrepresentation, particularly of those mesenchymal stem cells that they work. There’s a reason why, you have to pay for them, and, they’re not approved. The data that they actually perform a great function is not there. I don’t have any issue if somebody wants to do this. But I think the biggest issue is, be careful what you’re putting in your body. So you need to know about.
Alyward
How do you vetted?
Dr. Zon
I think you got to talk to your doctor and and actually find out. You should ask the person who’s injecting them into you. Where did they come from? What’s the source? Where they from? Adipose. Were they from bone marrow? Where are they made? And all those things would help me, generate an algorithm to say, I should do it or I shouldn’t do it. That particular stem cell population.
Dr. Blau
I think stem cells have tremendous potential, to help with our joints to to help with vision. To help with memory, learning all kinds of things. But we’re in early stages. It’s not ready for primetime. And I’m worried that these, rogue clinics are going to ruin it, because so far, it’s nothing bad has happened, but nothing good either. People go to the Dominican and get their knees injected with their fat stem cells. It doesn’t do any harm so far, but it doesn’t do any good either.
Dr. Zon
I should I should also say so. There’s a lot of good research in stem cell therapies now that come from induced pluripotent stem cells. These are cells that I could take from any of you and reprogram it to think it’s an embryo and character. Then it can make all the tissues of the body. And there’s excellent trials for Parkinson’s, for diabetes, for, degeneration of the eye, seizure disorders and brains. Those are all really true and are coming through now to phase three. And I think will be really good therapies.
Dr. Blau
They’re described in my book if you want to read them.
Alyward
We’ll take some questions from the audience.
Audience Member
This has been a really interesting discussion. Thank you both for your contributions to the field. There was a really interesting, publication in the last week, which you may have seen related to the naked mole rat. I don’t know if your socials have blown up about this. But the naked mole rat, lives ten times longer than other rodents. And there was a discovery related to cyclic AMP synthase that there may be four mutations that dramatically increase DNA repair. What do you think about this? How does it relate to potentially human aging and rejuvenation?
Dr. Zon
I think it’s super interesting. There’s a pathway of the cGAS pathway and traditionally that’s been linked to more DNA damage. Because the mole rat has these four amino acid changes, they actually prevent the DNA damage. It makes sense because the mole rat doesn’t get much cancer. And so it’s, I think it’s a very interesting thing. It’s particularly interesting because when we published a paper in science, this past year, we had, elements of the genome, that are, thought to be junk DNA, but they actually, get turned on and in the stem cells that are getting groomed, they have very high levels of this suggests, sting pathway as well as, these retroviral elements. There might be a protective mechanism of these things, and maybe it works through the underneath the signal like we’ve shown. So I was very interested in that paper.
Dr. Verdin in audience
I had an interesting question regarding the two pathways identified is are there any synergies between myostatin? What happens if you use the two together?
Dr. Blau
The gerozyme targets that pathway as well. So it acts on multiple pathways. It decreases TGF beta signaling. So when we when we inhibit the euro zone we inhibit myostatin. So it acts on the same pathway. In addition it also acts on after genes. So it turns off the catabolic enzymes that cause protein degradation. And it augments mitochondrial function turns on the mitochondrial genes. It does more than that. It’s, it’s multiple pathways in addition to which it acts on this, not just the myofibers, which is myostatin, but also in the stem cells, enhancing their function. And on the motor neurons that innervate the motor fibers. So a multiplicity of programs, which is one reason we think it could be really useful in sarcopenia, where so many things go wrong because it’s pleiotropic, and many of the drugs have failed because they targeted only one aspect of the disease.
Dr. Ornish in audience
First thing, thank you for such brilliant work is truly inspiring. When will the year two drugs be on the market?
Dr. Blau
Our drug just, went through phase one clinical trial and succeeded. So that’s good news. Safety, toxicity. The company is gearing up for phase two in multiple sites for sarcopenia. I’m really pleased that they’re doing sarcopenia and not orphan disease, because that can lead to pricing, as Lon mentioned, that is very high. Then it’s hard to bring it, to another price that would be available to your average older person, which is what I want. It would be a dream come true for me if that happened.
Dr. Zon
I would say I have a complicated answer, which Christine alluded to. The drug was supposed to be approved two weeks ago. But I did get this complete response letter. We’re waiting to find out what the FDA wants us to do about the Catalent site to have the manufacturing. Assuming that goes well, the drug will get approved. And, and so, you know, it should be available at us, you know, over the next year at some point. We have multiple versions also. You could have different drugs for different purposes too. That’s something that’s, being discussed. Thank you.
Dr. Blau
There are no drugs for muscle building at this point. So that’s that’s a huge step for them.
Alyward
Thank you Helen, Zon, this was great.