As we age, our bodies can lose muscle mass. Our muscle stem cells try to divide, but often die, and our strength ebbs. The result is higher increases of falling, fragility in our bones, a loss of cartilage, and decrease in our mobility culminating in “an inhibition of quality of life,” said Helen M. Blau, Ph.D., Stanford University’s Donald E. and Delia B. Baxter Foundation Professor, at DOC 2025.
Blau’s pioneering work has focused on stem cells and aging, which includes her research on the mechanisms behind how our muscles age. As the Director of the Baxter Laboratory for Stem Cell Biology, Blau and her team have uncovered a gerozyme — or an enzyme that drives aging— that is linked to this shift, which increases as we age and breaks down a molecule, prostaglandin E2 (PGE2), that is part of the body’s natural healing mechanism. PGE2 is critical for driving repairs of our muscles by stimulating muscle stem cells to divide and then restore injured muscle fibers. Building muscle strength through resistance training, for example, actually damages these fibers by design. Once repaired, they grow stronger. But this gerozyme inhibits this repair. Ibuprofen, Blau points out, does as well, by preventing PGE2 production.
Blau’s team found a drug that blocks the gerozyme, and showed that aged mice actually increase their muscle mass significantly (Science, 2021). A new study by Blau’s team has also shown that the blocking of this gerozyme leads to cartilage regeneration in a 2025 article published in Science.
“Should this translate to people, it could have a potent beneficial effect on those suffering from muscle wasting due to disuse, disease, or aging,” she said.
You can hear more from Dr. Blau as she outlines her research in the DOC 2025 session, “Aging, Stem Cells, and Rejuvenation,” in our video or read our lightly edited transcript below.
TRANSCRIPT:
Dr. Helen Blau
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. 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. 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. The goal of our work is to increase healthspan, or quality of life. 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. By age 60, 10% of people have what’s known as sarcopenia or debilitating loss of muscle strength. 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. 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. We’ve been interested in finding factors that could enhance the function of the stem cells. We found prostaglandin E2. It’s a metabolite natural metabolite part of the body’s natural healing mechanism. When there’s an injury there’s a wave of inflammation. Prostaglandin E2 is part of that wave. Notably, the synthesis of prostaglandin E2 is inhibited by drugs like ibuprofen, non-steroidal anti-inflammatory agents. You’ll see why that’s important. 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. 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. You should know that when you run a marathon or workout in the gym, you are creating little injuries. 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. We wondered what happens with aging. 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 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. 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. 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. 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. 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. 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. We identified a gerozyme 15KDA that degrades the PGE2 and is a hallmark of human muscle wasting. 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. 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.