Mike West - CEO of Age X Therapeutics

Mike West of Age X Therapeutics – Pluripotent Stem Cells, Telomerase & Human Regeneration: Simple BioTech Podcast #3

Dr. Michael D. West is the founder and CEO of AgeX Therapeutics, a biotechnology company whose mission is to develop and commercialize therapeutics aimed at treating the biological causes of aging to extend human health and life span. He was also the Founder and CEO of Geron, another biotech company focused on developing pharmaceutical treatments for the biological causes of aging. Dr. West is a leading researcher in the fields of stem cells and cellular aging.

According to Dr. West, why is research in the biotechnology of aging so exciting?

  • In our world of heightened age expectancy, we all confront the biological symptoms of aging.
  • West wants to understand what causes us to age and how we can unravel those causes.

Reproduction is the key to understanding aging.

  • Life doesn’t come from nothing; life comes from life, cells come from cells.
  • All the trillions of cells in your body can be traced back to one cell: the fertilized egg.
  • The components of fertilized eggs, sperm and egg, also known as germ cells, do not age as somatic cells
  • The question driving West’s age research: why do our somatic cells age and die, whereas reproductive cells do not?

Somatic cells: body cells; skin, bones,

Germ cells: reproductive cells.

The History of Cellular aging research

  • One of the earliest researchers was Leonard Hayflick, whose work began in the 1960’s
  • Hayflick discovered that somatic cells have a finite ability to replicate, which became know the as Hayflick limit.
  • One theory of aging: theshortening of the telomeres in somatic cells cause aging. Telomeres do not shorten in germ cells.

 Telomere: End part of the DNA, “caps” like the plastic tip on a shoelace.

  • Telomerase is an enzyme that makes telomeres.
  • Telomerase is turned off in somatic cells
  • West’s hypothesis: lack of telomerase is what leads to cell death.

The Beginning of Mike West’s work in aging research

  • West designed an experiment to the telomerase gene back on in somatic cells, hypothesizing that turning these gene back on would halt aging in these cells.
  • Many thought that one single gene would not control aging process.
  • Mike and Geron found that turning telomerase back on in somatic cells halted cell aging.

Telomerase gene is also turned back on in cancer cells

  • Cancer cells do not age, they are “immortal” and do not stop dividing.
  • No Hayflick limit in cancer cells.
  • Mike and Geron developed a test that could tell if telomerase was turned back on in cells They found that 90% of cancer cells have telomerase gene turned on.

Immortal cells: cells that do not stop dividing and do not age, such as germ cells and cancer cells.

  • Telomerase itsled does not cause cancer
    • Cancer is a multi-step transformation of a somatic cell
    • Equivalent to a runaway car with stuck accelerator, malfunctioning brakes, and infinite fuel
  • Nature makes cells mortal to prevent cancer.
    • Infinite fuel supply alone does not lead to cancer.
    • Giving a cell immortality does not necessarily lead to cancer: if the rest of the cell is working properly, cancer is not an issue.

Current AgeX Research: Pluripotent stem cells

  • Just after fertilization, the fertilized egg cell starts dividing and forms the inner cell mass, a raw material for life.
  • This inner cell mass is made of pluripotent stem cells

Pluripotent stem cells: Cells that have the potential to become any of the different kinds of cells in the human body. Different body tissues are made of different kinds of cells. Muscle tissue is made of muscle cells, which have a different structure and function than skin cells. Once a cell becomes muscle or skin, it cannot change to become a different type of cell and will only divide to produce the same type of cell. Pluripotent stem cells can become skin or muscle or any type of body cell. 

  • During the process on in vitro fertilization, during which embryos are created in a lab rather than in the human body, not every embryo created is used. The leftover cells, which are rich in pluripotent stem cells, are used to study pluripotent stem cells in vitro.
  • West’s research has been using these cells as platform for making replacement cells to treat aging.
  • They are essentially young cells for old people to repair the human body.
    • Pluripotent stem cells know how to form a human body.
    • Used to create human tissues in vitroand even new organs
  • This research developed into regenerative medicine, a whole field of medicine and research
    • Many treatments in development, but not yet available for treatment

These types of biotechnological developments give humans a lot of power over biological processes. What should we do with that power?

  • Mike thinks that we should only use them for medically necessary purposes.

What is AgeX working on right now?

  • PureStem: growing any cells with pluripotent stem cells
    • Focusing on brown adipose tissues and vascular cells
      • Currently in pre-clinical trials
      • Trials reveal evidence that these cells are beneficial.

Brown Adipose Tissue: Fat cells that turn food energy into body heat.

Vascular cells: Cells that form the vascular, or circulatory, system that carries blood and lymph throughout the body.

Preclinical trials: Prove to the FDA that they are safe and would be suitable to test in humans

  • Induced tissue regeneration
    • Cloning research revealed that there was something in egg cells that reverses cell aging.
    • West found genes in egg cells that are capable of acting like a time machine
    • These genes reprogram cells and can turn back the clock on cellular aging

AgeX is working on delivering telomerase and these genes into human cells to reverse aging.

What is meant by reversing aging in our cells?

  • Probably not a Benjamin Button scenario
    • Mechanisms that control the size of the human body are different from those that control aging.
  • Induce molecular mechanisms that would intrinsically repair the body.
    • For example, if you have a heart attack, the body would just regrow healthy tissue.

When will technology that AgeX is working on available to the public?

  • That is still unpredictable because it’s a very new, very powerful intervention.

How drastically do you see AgeX increasing life and health span?

  • Current maximum achievable lifespan: 120 years.
  • No intrinsic lifespan.
  • West thinks that aging will be eliminated in this century

What to watch for in biotechnology, according to Dr. West.

  • Uses of genetic engineering, both positive and negative.

What can someone do now to prevent aging?

  • Use common sense
  • Exercise, eat healthily, don’t smoke
  • Don’t worry about excess supplements
  • Wait for technologies that will target the mechanisms of aging themselves.
  • If you see a stem cell therapy available today, it is very likely not a science-based treatment.

To learn more about Dr. Michael West and AgeX, take a look that the AgeX YouTube channel.

Like what you hear? Click subscribe in Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Keep up with latest news, episodes, and Biotech updates on Instagram @SimpleBioTech. If you want to know which BioTech companies host James Ruhle is currently excited about, connect with him on Angel List, Angel.co/jamesruhle

Former President George Bush (00:00:01):
Embryonic STEM cell research offers both great promise and great pedal, so I have decided we must proceed with great care.

James (00:00:12):
What you just heard was George Bush, former president of the United States addressing the nation on live television about embryonic STEM cells. This happened in 2001 and what prompted George Bush to address the nation on this particular day was the successful isolation of embryonic STEM cells. Now, although this discovery could potentially be one of the largest scientific achievements in all of human history, George Bush and his administration were afraid of the potential ethical and moral ramifications, something like this could represent for the United States and the human race as a whole. On that day, George Bush decided to effectively ban the harvesting of any new embryonic STEM cells, but you continue to allow any private company that already had possession of them to continue their research and to continue advancing the field. The man I interviewed today was the man behind the company that first isolated these embryonic STEM cells. The man whose company and their discoveries prompted the president of the United States to address the nation on live television all the way back in 2001 the CEO of Age X therapeutics, the godfather of human regeneration, Mike West.

James (00:02:27):
Mike, I am so excited to have you on the podcast today. I’ve spent the past few weeks doing my due diligence, doing my research on Age X therapeutics and what you guys are working on. And all I can say is that the audience and myself included are in for a real treat today.

Mike (00:02:44):
Well that’s, that’s a kind thing for you to say. I’m looking forward to the discussion as well. If there’s not really a more exciting field to be in right now, I think then the biotechnology of aging, it’s a problem. It’s some people call it a disease, but it’s something that all of us have so everyone can relate to it.

James (00:03:01):
Yeah. And you know, I keep telling my friends, I keep telling basically everyone that will listen that the next 10 to 15 years even, I mean 20 years at maximum, what it means to be human is going to be completely different for a cultural perspective. This anti-aging stuff is going to change everything and I think that Age X is going to be a big part. Age X and all of the stuff that you guys are working on is going to be a big part of that chain. So before we dive too deep into the weeds here, I think it’d be a good idea for the audience if we just create a base layer of knowledge about the topics that we’re going to be discussing today in particular STEM cells, pluripotent STEM cells, telomerase, and how these all kind of work together.

Mike(00:03:55):
Well, can I kind of frame it in terms of the birds and the bees? If we don’t mind, I won’t talk about sex only peripherally. Um, but the birds and the bees. So reproduction I think is the key to understanding aging. And some people, you may have heard this idea, do you remember the book, the selfish gene, the Dawkins wrote some years ago? He proposed that, you know, the, the human body, human biology is really just a reflection of selfish DNA wanting to replicate itself. And that’s similar to a, the birds and the bees story that I want to relate right now. So if you’re a young aging researcher is, I was, when I entered the field, I was like, I don’t know, 27 or something older or younger than I am now anyway. And, um, where do you begin? It’s sort of like a Sherlock Holmes encountering a murder saying, where do you begin to unravel the mystery of what’s going on?

Mike (00:05:03):
What causes us to age and how can we find a way to intervene? And what are the first clues I picked up on? And this sort of detective, aunt, what relates to the birds and the bees? So if you think about it, life doesn’t come from nothing. You remember we were taught that in basic biology in high school, right? So I remember the idea of spontaneous generation. People used to think if you leave us some rotten fruit outside the, you know, the banana turns into a fly, you know, spontaneous generation of life. And of course then people figured out, no, no, no. Yeah, now it’s the slide laser that had gone the rotten banana and it becomes a larva. And then eventually a fly. And life comes from life, they say, and cells come from, cells were made of cells, trillions of little living, they’re all alive.

Mike (00:05:59):
Life on earth originally was just single cells floating around in an ocean and they kind of stuck together, uh, and eventually evolved in, you know, to human being. Well, they’re all alive. Life comes from life. Cells come from cells. So if you connected the dots of all of the trillions of cells in your body and went back in time to when you were developing in your mother’s womb, you’d come down to one cell and that was the fertilized egg. And when the sperm and the egg get together, that’s this much sex talk is, I’ll go into, maybe we go back before that those were cells in that person’s parents and you connect the dots back in time. Those were once a single cell or two there were in their parents and their parents before them. I think you see where I’m headed, there’s a lineage going back in time of cells that have been replicating and making humans for hundreds and hundreds of millions of years in an uninterrupted fashion because life always comes from live cells, comes from cells.

Mike (00:07:11):
So where I began in my surge, you mentioned STEM cells was the understand sort of the root of the human life. They branches out to make all these STEM cells in the body. What, how does life perpetuate itself indefinitely? And then the big question, the big question Mark, why is it that the cells in our body, which we call somatic cells mean Soma in Greek means body? Why is it that the sematic cells in our body inevitably age and die and just a few decades, where is the cells that made us have been proliferating for, you know, hundreds of millions of years. And I thought that by contrast thing, those two types of cells, the reproductive lineage to be called the germ line and then all the cells in our body that make up a human being, you know, I loved ones, the brain cells in the blood cells, in the bone cells, all of those are more whole and have a finite life span. And I began, that’s where I began trying to understand why it is that sematic cells age and can we somehow understand how the germline doesn’t. And by comparing the two, find a way to transfer the immortality, the germ germline into the Soma to try to stop aging, extend human lifespan, and potentially to abolish aging itself,

James (00:08:41):
right? And so that is where telomerase comes in,

Mike (00:08:45):
Right! So that was chapter one. So I was a researcher studying cell aging. So if you take some skin cells from your arm or something, you can grow them in the dish. In the laboratory dish, you know, your feet, there’s this like red Kool-Aid, you know, you put on top of them and they drink the Koolaid and replicate like these little pond water animals, but they’re your skin cells and they replicate. One becomes two, two becomes four and then you can move them to a new dish and they’ll replicate. And what a scientist named Leonard Hayflick discovered in the sixties 1960s that recently was that human cells of all different kinds in our body. Again, the sematic cells have a finite ability to replicate and we call that now in honor of him and his discovery, call it the Hayflick limit, or you know, cellular aging.

Mike (00:09:41):
And so I was studying cellular aging is a graduate student. And, uh, later on when I was in medical school, and I thought I knew what was causing it, I thought it was the Tila mirror. It was a theory first proposed by a wild eyed Russian theoretician and Alexi 11, a cough. He just dreamed this idea up that the ends of our DNA strands were wearing away, sort of like a fuse burning or candlewick burning. Every time a cell divides, the end of the DNA strand is getting shorter and shorter. And that was a clocking mechanism. And a, that region of the tumor is called the DNA is called the telomere means. And park in Greek can part that it does a DNA strands. It’s kind of like the plastic on shoe laces, you know, it’s the end of the DNA. And he proposed that Kayla murders were shortening in somatic cells, but then this immortal germline that keeps making babies young, that there was a special gene that was an immortalizing gene and it came to be called telomerase because it makes Tila mirrors and it winds this clock up.

Mike (00:11:03):
And, uh, I, my first company, I started like you being an entrepreneur, I started a company called Geron and at your on we spent a lot of money and a lot of effort, a lot of scientists worked very hard and we found the gene telomerase. And interestingly, the fun little angle here is the first human cells ever to be tested for to see if this gene work. A little bit of drama was Leonard Hayflick own skin cells. I happened to have his skin cells growing in the dish just when we had this gene. And uh, we put the gene on his cells and uh, we am, I called the experiment in my notebook, which I no longer have at the top. The page I wrote the immortals [inaudible] of Dr Hayflick cause I was confident that it would work. And it did.

James (00:12:02):
And that gene, that gene is telomerase.

Mike (00:12:06):
It’s the immortalizing gene. The gene is gene is on, cells don’t age if you, and it’s, but it’s turned off in our own cells are cartilage cells are blood cells, our brain cells all throughout the body to Soma. So as we live and cells divide in our lifetime, you know, a clock is ticking and all of our cells are careening towards the Hayflick limit and it’s a brick wall. It stops people from living forever. A lack of telomerase.

James (00:12:39):
Mike, I think you have a really good talent for explaining things in super easy to understand terms. I guess that’s a skill you kind of have to have if you’re the CEO of New York stock exchange traded company. But if I may, I’d like to just kind of go over everything that you’ve just said and kind of re-explain it the way that I’m understanding it in my own terms. So originally you saw these two germlines, the sperm and the egg.

Mike (00:13:09):
Yeah. There are germline cells, right? It’s a lineage of cells, you know? Yeah.

James (00:13:14):
And you observed that these germline cells there are different from the other cells in the body. These cells seemingly could replicate forever. They had no Hayflick limit. And for those that are unaware, the typical human cell can replicate about 50 times plus or minus. And if I’m not mistaken, once a cell reaches that Hayflick limit, that’s when it becomes a senescent cell.

Mike (00:13:42):
That’s right. So in essence sells a settled that’s reached the, it’s at the Hayflick limit can no longer divide. Right?

James (00:13:48):
So back in the 90s at Geron, which is a company that you started,

Mike (00:13:52):
yeah, that was the founder,

James (00:13:54):
You guys were the first company to isolate the telomerase gene, which essentially was a gene that immortalizes cells. And through that discovery, you took your buddy, Leonard Hayflick cells, you edited the genomes so that they would start expressing telomerase. And essentially you created the Immortalists nation of Leonard Hayflick, the immortalist nation of his cells. And through immortalizing his cells, you terminated the Hayflick limit.

Mike (00:14:31):
Well, you know, the joke was if you go into my YouTube channel, I’ve actually got an interview with Len, or we’re recounting the story, you know, and he just happened to be in the company and donated a little piece of skin for reasons. I’ll explain in that video. I won’t recount here, but I was a joke. I thought, you know, he said, you want some of my skin? And I said, well, sure, because I want to measure the Hayflick limit, the true height, like limit how many doublings your skin will go. We always talk about the Hayflick limit, let’s get the actual limit Hayflick cells. And it just so happened though that it was just that time when, um, when we had the gene cloned and you know, I have a lot of respect for Len. He’s still alive, still very active. And, uh, I told, you know, he deserves the honor his cells being the first to be, uh, immortalized by him, by the hand of man, so to speak. And, um, so yeah, so his cells were the first to see, uh, the expression of telomerase through human intervention. Right.

James (00:15:41):
That’s a great story. And I’m sure that was quite an honor for him.

Mike (00:15:44):
He enjoyed the experiment, but experiments normally don’t work. So at the time I was dating one of the scientists that I think played the most important role in finding the chain. Her name is Karen Chapman, and I’m married to her now. And, uh, we went out for dinner that night and had some wine and she said, uh, so tell me the truth kind of grinning. You know, you think that experiment’s actually going to work and I know what she was getting at in science. I mean, they call it research because you search and you search again and search again. Experiments in science is full of failure and testing the hypotheses that don’t work. And the chance that one gene, it could have been six genes, right? That one gene is turned off in somatic cells and padding that one gene back would stop the aging of cells.

Mike (00:16:48):
Len himself didn’t believe it would work. He thought that there were hundreds. He thought, well, he thought Len thought the aging of cells was where in terror it was this like entropy. You know, things fall apart, your car falls apart, the tires were on in your car. The cells get old and tired and worn out. And that was the prevailing iPod stasis. And what we were saying at German was, well, not really. There is a gene that is turned off very early in life and then there’s a car, a clock ticking and every cell except for the these germline cells that make babies and uh, they’re, you know, then then time bombs are going off as we get older. And those senescent cells cause our aging and death. And the idea that one gene was the sole cause it, you know, I, I agree that Karen was right to be skeptical, but I won the bet. She said when pigs fly and I’ve got a blind pig trophy on my desk today at work. Sometimes pigs do fly.

James (00:17:57):
That is very lovely story, Mike and even a bit romantic, the story behind the isolation of the telomerase gene, which brings me to the next thing that I actually, I really wanted to bring up because I saw in one of your interviews or I saw it on the website somewhere that I thought this was super interesting. For those that don’t know, cancer cells are essentially immortal cells. That’s what the problem is behind cancer cells is that they keep replicating forever. They keep replicating cancer cells. And one of the interesting things that you guys discovered about cancer cells is that they actually have the telomerase gene turned back.

Mike (00:18:40):
Aw, yeah. So there’s, um, at least one science fiction novel. It might be the sixth commandment. I’m not sure am read that story in many years. But it was about a gerontologist too who was doing research on aging. This is many years before we adjourn was started and so on. And uh, there was a, um, an old, old folk, so next to the research facility and a, some insurance person was coming to investigate because these older patients were all getting, um, peculiar cancers. Turns out the scientists had, um, in this story it found the immortality Janie and was, uh, testing it on people and causing cancer. Owns that all about cancer cells when they’re grown in the laboratory dish typically do not age. So we came to call those cells immortal cells. It’s a scientific term. It’s not meant to imply any theological concept. It’s a, you know, we’re not talking about the immortality of the soul or something.

Mike (00:19:51):
We’re just saying that the cells don’t age. They, they don’t stop dividing normal cells. Stop dividing age all, there’s never been, to my knowledge, a human normal cell other than if we get to talk about Clery potents themselves, germ culture, germline cells, blood cells, brain cells, any kind of cell from the body all have this Hayflick phenomenon. And when cells become cancer and you put them in the dish, they no longer age. So we say that David mortalized and no one knew the mechanism of that. Well we, that was easy for us to figure out early before we had the gene, we could tell if telomerase was turned on or not. And uh, we published back in 94 that over 90% of cancers who turned telomerase on. And so there was it Freddie Kroger or something, I’m not a big movie fan, but there’s the one movie you shoot him and he gets back up, but he keeps rising from the dead or whatever.

Mike (00:20:54):
You can’t kill him. Cancers are kind of like that. You hit him with radiation and chemotherapy and they just keep coming back. And the reason is the cells will not stop dividing. You can kill some cells but cancer cells, but they’ll replicate forever. And that’s what makes him so deadly. So doesn’t that mean the use of telomerase would cause cancer? No, actually it doesn’t. It’s a long, complicated discussion. Probably longer than we would want to talk about here. But I’ll just say cancer is a multiple step transformation of a normal cell into what causes cancer. It’s kind of like a runaway car. Oh, the accelerator is stuck down. So cells are dividing out of control. There’s no breaking mechanisms anymore in the cell, so they can’t stop. And uh, so the accelerator stock, the brake is broken in your car and it has an infinite fuel supply, so it’ll never stop running. And the infinite kills supply is a more telomerase nature, we think makes us mortal as a way to help prevent cancer. So the car will run out of gas. Uh, that’s one way to control a runaway car. That nature uses to help reduce the chances of cancer. But if the brakes are go are working normally in a car and the is working normally and you had an innocence that fuels supply that doesn’t make it a runaway car. Does that make sense?

James (00:22:36):
Yeah, that makes sense and it actually answers a question that I wanted to bring up later on when we talked about induced tissue regeneration, which is something you guys are working on because obviously when the thought of having cells that are immortal, that will replicate forever, you can’t help the think. There must be some sort of cancer risk here, but I think the, your explanation is actually really great and it’s a really good analogy as well. Using a car as the cell essentially. So as long as everything else in the car is working properly, as long as the brakes are working, as long as the steering wheel is working, then as long as those are working, if you add some fuel and unlimited fuel supply, it’s not going to get out of control. And that’s essentially how the cell works. As long as everything else in the cell is working properly, adding the fuel supply, AKA the telomerase to keep the cell going forever, it’s not going to cause a lot of problems. It’s not gonna cause cancer.

Mike (00:23:46):
Yeah. And on top of that, what almost all scientists who, a person that’s in this field of aging research believes is that telomerase is this amazing enzyme that’s lacking and causing cell aging and causing a lot of human aging. But what we would do is like a normal car, drive it into the gas station and then read up the fuel tank, not give you an incidence, real supply, which is reset tailor mirrors and then take telomerase away. So as we say, we would transiently temporarily express the gene to wind the clock back up in ourselves to make them younger and then, um, take the key to that clock away. And so there’s plenty, we think of what we call it as a therapeutic window. There’s plenty of opportunity to use telomerase, uh, especially when you’re, you’re very sick from an age related disease, coronary disease or something. There’s plenty of room to intervene at aging yet without causing cancer. At least that’s what we believe currently.

James (00:24:52):
So that is a pretty good place to start. I feel like we’ve laid a pretty solid foundation for the audience. So let’s go ahead and get started with what Age X is working on and let’s talk about pluripotent STEM cells and all the quite frankly crazy stuff you guys are doing with those.

Mike (00:25:15):
Yeah, so there’s three and a half major revolutions that I’ve been personally involved with. One, we just kind of talked about this Taylor marathon for if you were in the cell aging field and there are very many people in that field. Back when I was there that was absolutely unanticipated revolution and thought that cell aging was under control of of one gene. And it could be, you could immortalize a cell. I mean that was the only one left out of court before we’d actually proved how that was true. A second one. So what occurred to me was we should be able to actually capture this germline in the dish. It makes, as I’ve said it, babies are always born young. And we keep making baby people keep making babies and then their cells make more babies. And so on. As I previously mentioned. Well what if we could capture those magical cells, the germline in the dish?

Mike (00:26:25):
Potentially we could use them not to make people, but since just like babies are born young, we could use it to make just cell types that are born young, the young heart muscle, uh, for heart failure, young cartilage for your joints. You know, when you get older, the number one complaint in aging is the pain of arthritis. That’s the number one complaint. And, uh, you know, if we could rely on the surfaces of your joint with Dionne cartilage, that would be a really amazing, if we could make young cells for your midbrain for Parkinson’s disease, that, you know, where I’m going with this, right? Goes on and on and on. And um, some people just would like to make care for their head and everything else. So you’d talk about unmet needs in medicine. There’s never been a real practical way of making young replacement cells.

Mike (00:27:21):
Your car. If it wears out, you can go to a car parts store and get new spark plugs for an older car. You can get new tires put on, you know you can keep it in a car running indefinitely cause you can always get parts. The human body is as important as it is to all of us. We’ve never had a way of rebuilding the body and so I had this interest in trying to isolate the human germline in the dish and use it as a manufacturing platform to make young cells or any kind and you can’t use Berman egg because they don’t divide, but right after the egg is fertilized by a sperm, a cluster of cells form, it’s called the inner cell mass and it’s raw material for life and these cells, if you went in and divided that little cluster into two, you’ll get identical twins.

Mike (00:28:22):
That’s how they form. You can divide them again and get identical quadruplets. That even happens sometimes just naturally. It’s just these cells have not yet decided to make one person or two people or even a part of a person. Sometimes two of these will collide together and you’ll get a person that’s made of two different know DNA types. So anyway, these early cells of the inner cell mass, I felt they were being thrown away. When you use in vitro fertilization as is commonly done for people who have difficulty conceiving, children on their own excess fertilized egg cells were thrown away. And um, what I organized back in the mid nineties was a collaboration with some scientists, Roger Peterson that you CSF, James Thompson at the university of West Wisconsin at Madison and giant Gearhart at Johns Hopkins medical school. And this collaborative effort, we tried to capture these, broadly speaking, they’re called pluripotent STEM cells, meaning they could make the power or the potency to make everything in the body.

James (00:29:40):
Sorry to interrupt really quick, I just wanted to clarify. These STEM cells you’re talking about, are they the same as embryonic STEM cells?

Mike (00:29:48):
Yeah. So that they, if you culture them from the inner cell mass from the fertilized egg cell, they’re called embryonic STEM cells. Right. So when president Bush, president Bush introduced the country, really to these cells, his first address to the country from his home was on this discovery that I, this groups I pulled together. I was, so, it came very controversial, you know, you said, wow, this is, if you’re listening to his talk, president Bush was saying about how ethically problematic this was and a great ethical dilemma, but he felt that it could really change medicine. And the said, okay, so the ones that were already made, he would allow federal funds to be used to, um, use them in medicine. I don’t know if you remember all that debate. It was a big debate. And, um, it, so that became a kind of a national debate about these cells.

Mike (00:30:48):
But the scientific community realized for the first time, this is the first time we ever had the human germline in the dish. And you could study all of human development, the origination of heart tissue of the central nervous system, kidney development. It opened the door to just a normal new fields of medicine early, early on, before this was all public, I was presenting these ideas. I’m in a meeting and, uh, a scientist named bill Hazell teen, who used to be the CEO of human genome sciences, said this field is, needs a name. It should be called regenerative medicine. And it’s that name stuck. So now it’s a whole field of medicine, regenerative medicine. The concept is now we can, we have a pathway to make young cells of any kind of care, any tissue in the body parts supply store for the human body. We actually know how to do that now. And um, you know, a lot of these products are not yet available because it takes time to get FDA approval. But it’s a major area of research now for scientists around the world. So, you know, young, it’s a strategy to deal with aging. It’s a tool in the toolbox, young cells for old people to repair the human body.

James (00:32:14):
Let me ask you a question. With these pluripotent STEM cells, can these be used to grow entire organs? A replacement heart?

Mike (00:32:21):
Yeah, they can. So they’re so early in development. I mean, they know on their own, they know how to form a human body. And so they don’t make people or in a dish, but they make tissues and they self organize and uh, so you’ll see beating heart muscle on the dish. Then people have even seen, uh, you know, complex tissues like kidney tubules forming and so on. Yeah, they are very unusual in that respect. They’re capable of self organizing.

James (00:32:53):
So I just want to say for the audience, if you, if you’re not following along, these pluripotent STEM cells can literally create new organs on their own, whether it’s a heart muscle or I’ve, I would say a liver or, I mean really it can turn into any cell that the human body has. That is absolutely incredible.

Mike (00:33:19):
Well, it’s more incredible than that because as you point out, they can organize in the complex tissues, which cells and tissues from the adult human cannot do that anymore. But they have telomerase pluripotency STEM cells because they, as far as they’re concerned, they could still become a sperm and an egg. And so they haven’t committed themselves to mortality at that point. So because they’re the first, and to my knowledge, all night, normal at say normal because cancer cells are immortal, but they’re the first that only human normal cell ever isolated. That’s naturally immoral. That’s why I wrote a book about some of this, I call it the immortal cell because the quest was to find the naturally immortal cell and we’d found it with the Perricone. So it is the image germline. But now why is that important? It’s not just a scientific curiosity. If the cell will replicate indefinitely, it opens the door for scientists to go in and I wanted to say tinker with the DNA.

Mike (00:34:32):
That’s not the right word. Cause people will say, you know, scientists are playing games. It’s not really that you can make designed changes in the DNA that are designed to make supercharged cells or or or to correct genetic defects in the cell. But you can go in just like you do in a document on a computer, you know how you can do, find and replace and it word document. You know, if you were going to send me a letter and it was written to Bob, you can say fine Bob and replace it with Mike and with a keystroke, but all throughout the document I would find and replace. There is techniques like that in that we have in, in, in medical research, if we have a cell that we’re replicating, definitely it allows us to do find and replace so we can take the DNA and design it any way we want. I mean that literally we can now make any kind of human cell genetically engineered in any way. That’s a really powerful technology platform

James (00:35:40):
that is, it’s like you’re, you’re reading a page from a science fiction book that I would never believe so let me just clarify again for those that may not fully comprehend what you’re saying. Basically just a for a, let’s just say the heart. Okay. Let’s say you have had heart problems your whole life with these pluripotent STEM cells. Not only could they give new cells to your heart, potentially replace all the broken parts, they could genetically modify it so that now you have a better heart than normal. Now you have a heart that works significantly better, nor maybe have a, I mean, can I go as far as saying a heart of a super athlete?

Mike (00:36:26):
Yeah, well there’s some genes. The problem is evolution. You know, if we’re allowed to proceed for hundreds of millions of years, you know, presumably could turn the human species into something superhuman and what those changes are. It’s hard for scientists to know exactly how to buy. Can I come? I want to say it’s sort of tinker, but you know, we’re kind are tinkering because the DNA, the code of life that makes us from a single cell and makes us who we are gives us our eye color and everything else. How some of the genes are very easy to understand, but the coding language itself is really complicated. It’s like going into a computer code for Microsoft word again or something that, I use that analogy and trying to change the program when we didn’t write the original program. And uh, it’s tough, but there’s, you mentioned the super muscle thing.

Mike (00:37:21):
There’s one gene that we know called myostatin. If you go in and just take the gene away, they caught a knockout. If you go in and just remove the Jain, you get, um, double muscling. It’s called, you get, um, up to six times the muscle content in an animal that you’re normally would have. And uh, with no exercise, it’s not like the animal exercises Mars, it’s just the resting muscle mass. So, you know, we know how to make Arnold Schwarzenegger babies that never have to exercise, that kind of, that’s just an example of what could be done today.

James (00:38:03):
Mike, you know, me and a lot of my friends were very into fitness, very into working out. So you saying that it’s just music to my ears and I know that there’s going to be a lot of people out there that are interested in that.

Mike (00:38:19):
I’m not advocating it and I’m, I’m just saying that, you know, it’s reality and it’s, you know, there’s publications where for years we’ve had the mouse embryonic STEM cell long before we had the Yemen and the, this gene been, you know, knocked out, as I said, in mouse and you can see these mice, you know, there’s published papers on this double a muscle phenotype and you yeah, to have up to six times the muscle content. I’m a normal mouse. It looked like little mini mice.

James (00:38:49):
And so you just have these jacked mice walking around these alpha male mice in the group. Wow.

Mike (00:38:57):
We know it works in not just mice because there are rare, um, you know, cows that have this incredibly muscular phenotype. It’s just kind of ridiculous to look at those, you know, muscles bulging and they’d been sequenced. So we know it’s the, you know, the myostatin gene and so on. But that’s just one example. I mean, you know, a lot of people point to, because this is a doorway to introduce genetic modifications. Uh, people want to make dogs that glow in the dark, uh, for, for a pet. And in all kinds of crazy things. There’s a lot of things that science knows how to do. The question is what do we do with all these powerful technologies? I’m really an advocate of the medical uses of the technologies to alleviate human suffering rather than just tinkering life with the, with life for the sake of tinkering.

James (00:39:50):
I think you’re a hundred percent correct and I mean going forward, we need to use these powers for good for sure. But it is, you can’t help but just be excited about what the other possible potential is are out there.

Mike (00:40:01):
Yeah. And it’s a, I don’t even know where to begin. That’s the power of medical. Modern medical research is, um, very quickly outpaced, paced faster, you know, then, uh, even though wild-eyed science fiction writer would have written a few years ago,

James (00:40:19):
so, wow. That was, that’s uh, I’m blown away. My mind is absolutely blown right now. I want to ask you a little bit about some of what Age X is working on some of your guys’ products. Pure STEM in particular, although we’ve kind of gone over exactly what it does already. But pure STEM is basically what we’ve talked about, which is growing any type of cell from the pluripotent STEM cells repair. And you guys are focusing on Brown adipose tissue and vascular something.

Mike (00:40:49):
Yeah. Yeah. So a big problem in aging is metabolic imbalances. You know, we gain weight, central obesity type two diabetes. We think that’s due in large part to a loss of a anti-fat cell. Really. It’s called a fat cell, a Brown fat cell, but it’s actually works in reverse. It pulls fat out of the circulation and burns it to generate heat. They’re called Brown adipocytes and we know how to make those, remember pluripotent cells make everything. We figured out how to steer them into making just that LTI and just a vascular forming cells for like your heart. The heart attack is due to the lack of blood flow to heart. And we have some cells that can, you know, rebuild a vascular tree to or to the heart or other tissues like that. It needs increased blood flow. So, you know, we’re, we’re trying to implement, um, you know, his Woking back in time. We’ve, some of my previous companies, you know, we’ve, I have cells in human clinical trials even today for spinal cord injury and macular degeneration, the leading cause of blindness in aging. So, you know, we’re getting some of these products into human clinical trials and hopefully, you know, as soon as some of them will be approved for, for human application. But there, it’s really just the first halting steps really in this field we call regenerative medicine.

James (00:42:18):
Yeah, I did see on your website the Brown adipose tissue and avascular cells that you guys are working on are in preclinical trials. And what exactly does that mean? Pre trials?

Mike (00:42:29):
FDA is first and foremost concerned about safety cells. The transplantation of Suttles is historically been very safe, far more safe than the use of drugs. For instance, button nine out of 10 drugs fail in clinical trials and cells. Transplantations normally is safe. The FDA really is concerned about safety. That’s their number one concern. So we have to demonstrate in animals that the transplantation of these cells doesn’t. Uh, cause some kind of a health problem and those studies are what we call preclinical studies. So they’re, they’re typically animal based or sometimes based on laboratory experiments, but they’re all designed to demonstrate to the FTA that um, the product should be safe, uh, to at least begin a safety trial and in humans and to prove that they’re safe. Then you go to the efficacy to see do they actually benefit the patient?

James (00:43:32):
Well, I’ve got a few questions about that, but what if you can speak to it, what are your results so far with the animal trials? I mean, are there any results you can publicly reveal at this? At this time?

Mike (00:43:43):
Yeah, but they were a public company so we don’t disclose that which we’ve published on or somehow announced. What I can say is that there’s evidence, considerable amount of evidence, uh, for both cell types that they’re beneficial work out of the, um, Harvard has a thing called the Joslin diabetes center and they, with age, you lose this Brown fat and it leads to what we believe is this accumulation of fat around your waist. And then insulin insensitivity or so adult onset diabetes. That’s a real problem by the way, not just obesity, but type two diabetes. It has a lot of bad side effects including heart disease

James (00:44:28):
as humans. At what age do we typically start to a significant amount of out of that Brown adipose tissue?

Mike (00:44:33):
Yeah. You know, it’s, it’s, it’s kind of linear, you know, it’s progressive with time. So we have a lot of it when we’re born. And uh, some people believe that mammals, they, when they’re born, they don’t know if you’ve ever seen little pups dogs or mice are called pups as well. They don’t have much hair on them, you know, they’re kind of like these little skinny little things. And when mom leaves, they could quickly die just from being cold, especially in colder climates. So animals, including humans, when we’re first born, we have a lot of this Brown adipose tissue and our chest region and we get cold and it’s just like a thermostat that turns on your heater. When you’re feel cold, the brain sends signal to the Brown fat and it literally generates heat. It’s like a furnace in the body and, but you lose that as you get older and they re the result is without this tissue, you cannot absorb glucose and circulating fat the way you could when you’re younger. And so, uh, you know, your glucose can go out of control, you’re circulating glucose levels and a fat can start accumulating like in your coronary arteries. So really, uh, it positing fat, inappropriate place. That’s what a coronary disease is. Cluster all we hear about.

James (00:45:59):
Right. That makes sense. And so once you guys, and hopefully if you guys get all the way through clinical trials with your targeting the Brown adipose tissue targeting the vascular stuff, how easy is it to then use that same technology and get things through, let’s say art tissue?

Mike (00:46:18):
So what the first product ever made from these cells or cells for spinal cord injury that was done at my first company, German. It was the largest, most extensive preclinical package ever presented to the FDA in history of the FDA. It was so much work was required. It was a really heroic effort by the juror on team. And, uh, but every new product we approached the FDA on got easier and easier and easier. So now their products are, they’re still, you know, they still take years. Um, a lot of capitals had to be developed, but you know, applying this to regenerating the heart or for Parkinson’s and so on has, um, you know, relatively straightforward. It’s not unlike drug development at this point.

James (00:47:11):
That’s great news. And for the induced tissue regeneration. Now that’s the telomerase part of your company. Correct?

Mike (00:47:18):
Well, you, you said you were kind of amazed by the science now. Now I’m going to lose all you and your listeners, because you’re going to say no those. Yeah, I was of going along with this guy, you know, this is kind of niche stuff. Yeah. I Googled telomeres and telomerase, so yeah. Wow. Yeah. Some people are, you know, our old collaborators got Nobel prizes for this Blackburn, Carol Greider, stuff like that. Yeah. Wow. That looks real. Yeah, no bell Kobe thought so. Yeah. Then I’m gonna tell you about ITR and you say, ah, okay, so this guy went off the rails.

Mike (00:47:52):
Let me tell you

Mike (00:47:53):
CRS story. Let me tell you this story. It’s not a story. It’s real, but it’s new and you’re not going to find a lot about it online. There was actually just the article written in the New York times a few days ago. I think Nicholas Wade wrote it and um, they cited, uh, Lenny Guarente at MIT saying, you know this, this is a big deal. So I mean there is, it’s starting to get out there. So I was like, what’s the deal? I began with Dolly the sheep back to the birds and the bees here. So normally life begins with a fertilized egg cause we said, well, it turns out something that no one thought would ever work. If you take a cell from the body, a sematic cell, that ages and is a mortal, right, it’s differentiated to, it’s now a skin cell or a heart cell or whatever. If you take that cell and it’s a DNA, it’s a little blueprint of life and you put it into an egg cell, the egg cell will act like a time machine and it reverses the aging of that somatic cell and takes it back to an embryonic state.

Mike (00:49:07):
And if you put that cell into a uterus, you can generate an animal identical to where that cell came from. So if I, that’s calling of course, somatic cell, nuclear transfer, SCN T. so Donnelly was clone from a cell from breast tissue. They named her after Dolly pardon to typical tumor overworked scientists. So this what was once a breast epithelial cell was put into an Xcel and the cell was taken back in time and a young lamb was born. And I was really entranced by, I thought that this was reversing aging itself. I bought the U S cloning effort and it was a company called advanced cell technology and the animal cloning company, my old company Jaron, which I had left, but the a Dolly Roslyn company, and they published in nature, those prestigious magazine that it didn’t reverse aging. So Dolly was in data Lam, but she was a lamb and she was a shape in Lamb’s clothing.

Mike (00:50:30):
She was actually born old. And then a lot of people believe that that’s kind of a myth out there. We published a year later in the year 2000 and science, another kind of competing journal, the a in CO’s, at least somatic cell nuclear transfer. When you take a aged cell from the body and you put it into next cell, the egg cell acts like a time machine. And we showed that at reset Taylor Merz, it activated telomerase and rewound the clock and the resort resulting baby cow was born young. Totally normally young. Now what do I tell you? That story, I thought that was truly magic on multiple dimensions. One that the process of making a body, that arrow, we call it development could be turned into reverse. I mean, why would it go? It never goes in reverse in nature. How could that possibly be true? And secondly that something in the XL reverses aging and the truest of sense.

Mike (00:51:46):
I had to study this. And so beginning around, um, 88, 89, you know, that’s all I worked on for years and years and years. And we published in 2001 the first, um, right, right around the time that, uh, bullshit approved, uh, talked about the Emmerich STEM cells. We published the human nuclear transfer taking a human cell in a ride in a human XL or human time machine that was a little controversial. President Bush vehemently disagreed with us, ordered the patent office to remove one of our patents after it issued. And we were kind of at war was president Bush on that issue. Our intent, I think was misunderstood. Why not was we weren’t in trying to clone people. We were trying to clone cells and I wanted to find a way to reverse the aging of cells. Well, over the years we found the molecules in the egg cell better light telomerase, those capable of memorializing a cell.

Mike (00:53:02):
We found the genes. In this case, it was several genes that are capable of acting like a time machine. So, just like if you put telomerase into land Hayflick’s cell, it can, uh, extend the Taylorism cell and immortalize the cells by putting these ITR genes, we call it induced tissue regeneration, ITR. It can take cells back in time. And what we’re doing is developing it to take cells back in time in the human body. So we’re working on delivering telomerase and these reprogramming Janes as we call them, into the human body to take yourselves literally back in time to reverse the aging of cells and tissues in the body in the truest and pull us sense of the word. Is that possible? Well, we haven’t published much of our data. We publish some at Age X. We publish some basic science, but we have two competitors in the field.

Mike (00:54:20):
Friendly competitors. I would say one is turn T, U R N like turning back the clock. We are a group out of Stanford. They just published this paper, which was written up in the New York times. And uh, they’re seeing that these genes reverse the aging of tissues of various kinds. The other competing effort is David Sinclair’s group of Harvard medical school. And um, they publish. When you put these genes into the eye, you can reverse the aging of the eye and re and deuce a characteristic that cells and tissues have when you’re very young. When the body is first forming to repair, naturally repair itself in a very profound way. And so that’s why I call it and do tissue regeneration or ITR. This technology is the most profound science I’ve ever encountered in my life and I believe it’s going to be really history in the making.

Mike (00:55:34):
What’s no one’s expecting to happen. Knowing that I think no one thought we’d ever reverse the aging of cells with Tila mirrors, core cloning, that you could actually clone an animal, but actually reverse the aging process. I mean literally in the body of an animal or him aging researchers never thought that was possible. Slow aging shore. We knew we could do that. Extend him a lifespan or animal lifespan. We’ve known we could do that for years, 30% or something, but reverse the aging banana more or tissue. That’s an eye opener. I’m sure the average listener would thank God that just simply can’t be true. Hope, but it is true and that’s what the public will be hearing about, I’m sure over the next few years as papers are published.

Mike (00:56:33):
And so let me ask you to put this, put the significance of this into practical terms so people can really wrap their mind around it. When you say reversing ourselves, reversing the aging of ourselves, I mean, what exactly does that mean? Are we saying that with this therapy I’ll be able to go back to being a child or what exactly do you mean by us?

Mike (00:56:56):
No, so, well I guess we don’t know because we haven’t done a name and, but I wouldn’t think so. The growth pathways appear to us in our are, the modern medical technologies are incredibly powerful. You know, with this RNA sequencing and everything being, it’s just so much data and it appears that the, the mechanisms that control the size of the human body are separate mechanisms from those that are controlling aging. At one point, some scientists thought maybe they were the same and they thought that aging was sort of a mechanism for us from becoming giants. We stopped growing when we reached adulthood and that that same process was causing us to age. I don’t think that’s true. And I think most that’s true. So if we reverse the aging of our tissue, we don’t think you would literally get smaller and smaller and become a baby.

Mike (00:58:01):
What we think is what would happen is that you would, the way we’re designing this technology is that we would, you would induce molecular mechanisms that really you don’t even have when you’re born intrinsic ability to repair your body. Scarless li like in a heart attack early in development, you have a heart attack, the body just regrow his new heart muscle and we believe we can reawaken that and reverse and add back tail of marijuana through the use of telomerase, but allow the body to kill off old cells naturally and replace them with young healthy cells in a healthy state without regressing size and development. We think that’s it. That’s a pathway. It’s commonly called the hippo pathway, like the hippopotamus that controls body size. We think it’s different. So, but you know how all this would work is this is entirely new technology and write off just kind of giving you a glimpse where the sciences at the moment and uh, their current animal data and looks extraordinary and the science is very strong and we’re quite excited about it.

James (00:59:29):
I’m excited about it as well. Mike, this is, this is really, really cool stuff. So let me make sure that I’m falling along with everything that you’ve said so far correctly. Basically. I mean, but it’s not going to be Benjamin button. Not likely, but it’s, but what it is going to be is, you know, if we have chronic injuries, if we have chronic, you get a heart attack. I mean anything like that that happens, just tissue regeneration, it will be able to heal you 100%

Mike (01:00:02):
that’s what we’re aiming at. I think it’s possible we had that. We know, let me put it this way, we know we, it’s well established that we can reverse the aging of cells all the way back to the beginning of life. Right? You know that right? That’s, that’s called induced. Not tissue regeneration but induced pluripotency IPS cells. So I can take yourselves back to the day six of development and then make beating heart muscle in the dish. And that your heart muscle that you had and the first few weeks when your body was forming. We know that that’s well established science.

James (01:00:45):
Sorry, but that is also insane. Yeah, it’s just so cool. But go ahead. I know

Mike (01:00:49):
it’s insane. It’s cloning, but it’s, I used to call it analytical cloning. It’s cloning without using the Excel. It’s using molecules to do all the work and it’s called induce per phone. So we, so we know that we can reverse time zero and truly make all these age markers go in reverse and take you all the way back to the cells you were born from. Now, if I did that in you, you would just be this green pile of cells. You would lose all of your, your differentiated cells, you’d be slime. And uh, that’s not a good thing. So instead what I’m describing here is taking the train ride instead of back in time, all the way back to the beginning of life. Jumping off the train partway, the majority of scientists call it partial reprogramming. And that’s the concept. You’re taking this, um, miracle, a reprogramming of taking yourself back to the beginning of life, but you’re only taking it partway and you’re jumping off the train.

Mike (01:01:56):
And, um, like I said, we all had, when our bodies were first forming, we had this amazing ability to repair a tissue. If you go into a, um, a baby that’s just forming and its mother’s womb and you cut the skin in 72 hours, it’s the skin is completely normal and appearance scarless li. And if you took a chunk out of their heart for having to do the heart attack and of course to send a mouse or something that a human, it can regenerate, the spinal cord can regenerate. And [inaudible] we know that from some data. So what we’re interested in doing is taking, um, cells in your body back to that early stage and then letting them go back and forward and time again. And also resetting to them are like, why am I optimistic about the outcome? Because nature shows us that such a reactivation of regeneration and see the mirrors can soar to aging.

Mike (01:03:07):
So some animals can regenerate profoundly and have telomerase all the time and they don’t get cancer and they don’t age. So you know, these little planaria have you seen these little flatworms right? And to buggy eyes and crawl around. You can cut their head off and their tail will grow a new head and a head will grow new tail. And you can do that forever. They’re said to be immortal under the edge of the knife. And they can regenerate. They have telomerase and they just keep going and they don’t, there’s no aging and those animals and there’s more complex animals. There’s a animal and I think it’s a Slovenia called the Omar O L M and it can regenerate and um, presumably as telomerase. So I don’t see definitive data yet on that. We know it can live at least a hundred years and most people think it’s in her mortal vertebra animal. So the ability to regenerate and for ourselves to replicate without a Hayflick limit, we think are the two most profound means to intervene in aging. Been found to date. That isn’t to say, you know, there’s other strategies there may be, but animals that have the ability to regenerate and can do it endlessly typically don’t age. So regardless, these will be very important in medicine. Yeah, that’d be the ability to regrow a heart after a heart attack and the ability to induce that would be all by itself, you know, a very important advance of course.

James (01:04:50):
Yeah. And one thing that I saw, and again, one of your videos and all of these videos that I’ve been watching, I’ll include them in the podcast show notes for anyone that’s interested because there’s some really, really cool stuff and the Age X therapeutics YouTube channel. But one thing that I saw, I think it was in your undoing aging talk, was that you mentioned that all of these mechanisms of aging that a lot of people are targeting and trying to tweak and figure out mTOR and PK

James (01:05:18):
what your theory is, what the Age X theory is. Is that really the reason why those are so beneficial for humans is because they ultimately enabled tissue regeneration, which is exactly what you’re working on.

Mike (01:05:33):
Yeah. Yeah. We believe that that’s true and they, I think researchers will be quick to point out. Kathleen Kenyon wrote an article in nature genetics, I think nature biotech, maybe it was, and she was talking about, you know, she’s a Calico now, you know, Google’s anti-aging company and she, in this article she was talking about Dow scientists by studying animals like these worms, C elegans and so on. They found genes that will extend lifespan. As I said, that’s, that’s old hat or we’ve been gerontologists had been extending the lifespan of animals for years and we think that provides important clues about aging and it would fall on these genes. You know, like the growth hormone pathways. Am tore, you mentioned and so on. But in this article she says, you know about still what we don’t know is why tinkering again with those pathways? Do we extend the aging life span of an animal?

Mike (01:06:37):
How’s it actually, why does it impact aging? And, uh, that’s been an unanswered question. Well, what will we think is that the normally nature turns off these regenerative pathways and they can be reawakened in certain kinds of stress. So for many millions of years, we haven’t had the luxury of agriculture and the wealth that we have in today’s world. And there was common, like for all animals faced famine cycles, right? There’d be a long summer, winter, whatever, and we wouldn’t have enough date. And so what the body does in those situations is it starts sort of catabolising itself first. You burn the fat, of course, when you’re starving and you lose, that’s what fat is. It’s a means of storing energy for a feast, famine. And then you’ll start sort of doing the same with muscle, you actually start losing muscle mass. You’re kind of eating your own muscle in a sense.

Mike (01:07:44):
But let’s say that you go through that famine cycle and now it’s springtime and there’s abundant fish and fruit and everything else you chow down. That’s the feast part of the cycle. And, but the body needs to be able to regenerate the tissue that has used up in the famine. And so nature kind of turns that back on. It turns on regeneration a bit to allow you to rebuild your muscle mass again. And of course fat easily grows. That’s never been a problem for humans. And, um, yeah, so if you dietary, if you restrict the dietary intake of the human and most animals, you extend a longevity and we think it’s by natures reawakening some of these regenerative pathways and you, that’s part, it’s kind of complex biology. But so we’re, what we’re doing, we believe in the gerontology community and these meetings, people working on the different aspects of aging are kind of like the set up, the proverbial story of blindfolded people touching an elephant.

Mike (01:08:52):
You know, and some have a hold at the tail and some have a hold of the trunk and they say it’s a, it’s like a rope. No, it’s like a trunk of a tree. We were all looking at different aspects of aging, but we’re comparing, our notes are listing the blindfolds and realizing actually there’s a unified theory of aging here in rural studying the same thing. And uh, we’re starting to put the puzzle pieces together to a really profound understanding of how we age and then of course, powerful tools to really get at the central mechanisms and point the arrow and reverse.

James (01:09:29):
When I first got into this whole anti-aging thing, I kind of, well basically I saw David Sinclair on Joe Rogan and I kind of went through the, as I would call it, the David Sinclair protocol. I bought a bunch of NAD boosters. I started using the sauna and I started fasting. And of course all of those things are extremely good for you and healthy for you. But as I’ve talked to more aging experts, they really aren’t going to move the needle that much. And for those that aren’t aware of the pathways that I was just talking about, an PK, IGF one, all those aging pathways, fasting and sauna, all of that works on those pathways. But ultimately what’s really gonna move the needle because those things, from what I understand in a best case scenario may increase your lifespan by three to five years. That, am I correct in that?

Mike (01:10:23):
Yeah. Well we don’t know. Of course we’re guessing based on will data, but right. You know, you’re looking at, you know, a modest impact on longevity.

James (01:10:31):
Exactly. Exactly. And so people come to me cause you know, in my community they kind of know me as I keep up to date as much as possible with this anti-aging stuff. And the thing I’ve learned the most is that yeah, that stuff’s not going to do much, but this stuff that’s coming out in the next five to 10 years that’s going to move the needle. And I guess that brings me my next question is in a best case scenario, when would, what Age X is working on be available to the public?

Mike (01:11:02):
I really like giving straight answers to things. I hate it when people waffle. But the true answer to that, it’s entirely dependent on how many are, are working on it. You know, it’s, it’s like, you know, Kennedy saying we’re going to go to the moon in this generation while will we, what year will it be? What be in 1969, 1967, you know, or will be the 1970s. So it really depends on how many people we have formulations in our hands. A turn has and Davidson Clara groups has this part they call partial reprogramming. And I call it induced tissue regeneration. Different names for basically the same thing. And um, we both, we all have formulations that could theoretically be used in humans today, but you know, we won’t, I won’t anyway, put it into him. And today, and you know, I intend to work with FDA and you know, we’ve got all, this is an entirely new, I don’t know how to stress this enough.

Mike (01:12:05):
This is a really powerful thing we’re talking about and it’s kind of like a, you know, Adam bomb, I mean, this completely reprograms the DNA in a cell. This isn’t subtle. This is a very powerful intervention. So you know, the burden on us to prove safety is rather large. And when this will be available to humans in a clinical trial setting or to be launched as a product that can be bought by visiting your doctor’s entirely dependent on many people. And it’s difficult for me to project it at this point. It’s age X is a very small company and we did a pharmaceutical partners or, or some other means to get a lot of people to make it happen that, you know, will happen in the lifetime of many now living inevitably. But, um, I couldn’t, I wouldn’t even want to try to project a year at this point.

James (01:13:04):
That’s fair. So could be five years, could be a hundred years somewhere in that timeline somehow.

Mike (01:13:10):
No, no, not a a hundred. Yeah, we’re two. We’re talking earliest five years and with massive effort. And um, I would say on the outside this, this will be in him, even at the slowest would be in 15, 20 years. And we’re not talking about a hundred years cause I mean the formulations are already in existence. It’s in a like a drawing in medicine and in drug development oftentimes you have an understanding about something like cancer and you start searching for a drug that will hit the target and potentially be used as a cancer therapy. And so that’s the beginning of discovery research, you know, where you’re just searching for the agent or we were beyond that. We have things that could be used therapeutically today. So you know, it’s, it’s a question of yeah, more of like, uh, there’s still discovery research that needs to be done for sure. But we’re mostly talking about the challenges of demonstrating safety and animal likely preclinical studies and then at the beginning of a human clinical trial,

James (01:14:20):
well it’s a ways off, but I mean it’s going to change everything.

Mike (01:14:25):
Yeah. Let me just say, it will change everything. It really will change everything. They, how we think about degenerative diseases. And then of course aging is going to forever change based on these, some of these discoveries we’ve been talking about today and it really changes the whole paradigm of how we think about aging.

James (01:14:45):
I think you’ve done an amazing job explaining this to cause a lot. I mean 90% of the audience, 99% of the audience is people who are just casually interested and I think you’ve done such an amazing job today getting me excited and I think a ton of people are going to get really excited about this and um, you guys are publicly traded just saying you can invest in this company right now on the New York stock exchange

Mike (01:15:14):
Connections. You mentioned being public. We have filings with the sec, you know, anyone looking at the company, you should carefully review all of our filings. They carefully reviewed them before making any investment in the company. Please,

James (01:15:29):
of course this is not investment advice, but it is still pure, a super exciting company. I want to finish things off if I can with just asking you a few fun questions if you don’t mind.

Mike(01:15:40):
Oh yeah, sure. Of course.

James (01:15:41):
First of all, let’s, let’s really, I want to talk, best case scenario, I want to talk if Age X knocks everything out of the park with the pure STEM, with the ICR, with everything that you guys are working on, how drastically do you see this increasing human life and health span?

Mike (01:16:01):
Yeah. For years as a young dermatologist, it was clear to me, people in the field of aging research, it was a verboten to talk about the answers. It’s your question. And it was unspoken rule, but it was a, it was a very clear rule. I never understood that role because it’s a logical question, right? And part of it might be, there’s a lot of quack medicine out there and I think, uh, you know, I would predict here that as the science becomes more commonly known as science papers are published and people, those blessing to programs such as what you’re putting on and so on, people will start this more and more needles, the fake medicine, quack medicine. The clinics say, come get it now. You know, I come get reprogramming now will be everywhere. And I think there’s a reticence in the aging community to raise hopes and then have people go out and spend their money with the fraudsters out there naming a particular group or thing.

Mike (01:17:12):
And so on the other hand, scientists I think have a moral obligation to try to communicate where science is and where it’s headed. I think we’ve largely not done well in that regard. I think the public is woefully unaware a lot of the science going on in medical research. And so I feel I need to be, you know, quite transparent about this. I don’t believe that there’s an intrinsic, a limit to human lifespan that there needs to be. There certainly is now 120 years or so is the upper limit. That’s what we call lifespan life expectancy is when half or a group of people have died. So that’s the average time people that have you here, you know, it’s in the seven days differing men and women lifespan. The maximum achievable lifespan is about 120 but that’s entirely a brick wall that results from this unique biology in our sematic cells.

Mike (01:18:27):
As I said, we’re made of cells that had been proliferating for billions of years in the past. And then suddenly within a few decades, boom, they’ll age and die. It’s a unique characteristic, the cells in our body and we know we can reprogram a sematic cell back to the germline and reawaken the immortalizing gene telomerase and, um, these regenerative pathways that allow the body to repair itself indefinitely. So I don’t believe there’s intrinsic limit to human life span. They say actuarials that studying life insurance and things say if we eliminated the biology of aging with drugs and technologies such as we’ve been discussing humans with probably live somewhere in the realm of six to 700 years. And in today’s world, with the risks we have on average, life expectancy would probably be about six to 700 years. And then we’d get hit by a bus or something killed by coronavirus something. And why are we talking about immortality? Not likely. Yeah. Mortality by definition is never achievable. Right? You never get there. But are we talking about eliminating aging? Yeah, I mean I, I’ll break the code of a gerontologist and say, I think aging is inevitably going to be eliminated and I think it will, I think in this century, people listening to this podcast many decades later in this century then will say, yeah, you know, these guys saw this coming. Yeah, the end of aging probably is in our century.

James (01:20:22):
Amazing. And with what you guys are working on the, I mean, the ability to induce tissue regeneration when things go bad, when you have injuries, when you have just things that pop up as you age. And then on top of that, what you guys are doing to pluripotent STEM cells, being able to just regrow organs that may go completely haywire. I’m inclined to believe what you’re, what you’re saying.

Mike (01:20:49):
Wow. It’s helps. So I haven’t said anything actually that’s controversial. And the scientists that are studying aging, I mean there might be this or that one that would disagree, but that’s this Gulf of knowledge is the gerontologists I talked to, I mean I do a reality check sometimes. I won’t name names, but I asked some well known gerontologists that are highly regarded and well known and that they’re in some cases, competitors. That’s a reality check. Would you agree with me? This is where we’re at. I mean, yeah, of course there’s this Gulf of knowledge, the juror intelligence. No, all of these things are real and are happening and then the public isn’t even aware of a lot of it. So, um, you know, I would hope that people who are interested in this, we’ll just do a little research online and uh, and educate themselves further on it. It’s, uh, it’s fascinating history and the making my role and it’s just a part of the, you know, there’s many very dedicated and hardworking scientists. It’s not just Mike West out there. There’s a lot of hard work being done by a lot of people here, which have, we don’t have time to name all these people.

James (01:21:59):
Well, you’ve definitely been a massive artifice for sure. And I think that it speaks volumes that in the aging community and the people that are actually in the weeds that are working, it isn’t a controversial thing to say that there is no potential limit to biological aging. That, and I think that’s, that speaks volumes. That statement alone speaks volumes.

Mike (01:22:23):
Yeah. If it were where and terror it’d be entropy and that you’d say, well that’s a second law of thermodynamics such as part of nature. But we know that that the second law does not apply to living organisms. Yeah, we just found that.

James (01:22:39):
So the second question I wanted to ask you was what is the most scifi like thing you are excited about in the biotech industry right now? But I feel like our conversation has already gotten pretty scifi. Is there anything that is even another level above what we’ve talked about that’s potentially on the horizon? Yeah. Yeah.

Mike (01:22:56):
You don’t wanna say fi more at I what I think OSI fi, I guess this isn’t exactly scifi, but I have, dear friend of mine is cook. He wrote coma, you know, uh, rice, he’s medical thrillers and you know, he’s a friend of mine and I, I’ve asked Robin, why is it that the biotech scientist, whatever is always the bad guy. I mean maybe even an intended good, but it always goes wrong, you know, and then at least some kind of Andromeda strain or some kind of monster or some something goes terribly wrong and they said, what bike? And I’m, that’s a formula that makes great stories. When I think of Saifai, I just naturally think we’re kind of the wild and crazy thing. And yeah, these thought, it’s so easy, relatively easy. That is to dream and use your imagination and to think how these technologies could be used to alleviate human suffering.

Mike (01:23:57):
For instance, just out of the hat, just to give an example, a HIV infection AIDS, you’ve probably heard of the Berlin patient. Uh, it was a patient that was treated with a bone marrow STEM cell transplant and it absolutely cured him. They can’t find the virus anymore in his body. There’s cells that can be in transplanted into patients and Alto actually be resistant to AIDS. And destroy the virus. And we can imagine you could actually do this if you had the money and the resources you could use these technologies we talked about today, make genetically engineered blood forming cells that would be transplantable into an AIDS patient and they could, or an HIV infected patient and they could read the body of the virus and be cured of the disease. Not just one example, but you could also imagine wild and crazy stuff. You could genetically engineer, you know, soldiers with this double muscling phenotype, sort of an area and race.

Mike (01:25:05):
You could, uh, use it, um, to make, there’s a, um, a neurotransmitter that in animals when you altered the junior, you increased the intelligence of the animal. Conceivably, you could tinker with human intelligence, as I mentioned, make dogs that glow in the dark and you wouldn’t have to put a collar on them. When you take them for a walk at night, they would light up the street in front of you cause they glowed in the dark. You know, there’s crazy stuff we could do. And that’s where I had someone come to me once and I wanted to clone a dog and name him Glover and a glowing dog. And I said, well, why? And he said, why do you gonna be fun to take it to a party? This is the kind of frivolous thing. The more I worry that humanity would with these immense powers that were getting in science and medicine, where the sort of the science harebrained may be even intending, well, but turning into something terrible could go wrong.

Mike (01:26:10):
I think if we focus on alleviating human suffering, improving quality and length of life, I think these things are solidly in the human tradition. They’re the compassionate use of science and technology. I think that’s a compass needle. I will follow all day long, but I’m, I’m certain there will be people out there for whatever motivation will realize that they can do mischief with this new science. And um, it doesn’t take a lot of imagination to think of different inventions that can be used than many people write novels and stories about how the science could be misused. So yeah, it’s not all science fiction. I think some of what will become science reality on the negative side as well as the positive side.

James (01:27:04):
Well you just got to hope for the goodness and humankind to make good use of this stuff. And obviously there’s a ton of people already working on that, including yourself.

Mike (01:27:14):
Yup. Everyone. I though the listeners I ever, everyone I know in medical research, 99.9% of them have very good intentions and are focused on life threatening diseases that cause people to software or our loved ones to suffer ourselves to suffer. And uh, they should take some comfort in that. It’s rare that I encounter, uh, wild-eyed Koch that wants to do something crazy. It’s really quite rare.

James (01:27:44):
Yeah. The mad scientist seems to be a trope that really maybe doesn’t exist in reality that much. At least if they do

Mike (01:27:52):
sells novels. Yeah. It’s just, I’ve been in the field like this cloning field that was really controversial and everyone thought we were going to clone the vehicles and bring them back and Lucy and Ricky and all kinds of stuff. But, um, then there were a couple kind of fringe people talking about such things, but people were focused on, uh, on medicine and I’m doing good.

James (01:28:21):
Super exciting stuff. Mike, I just have one more question. This is kind of a, maybe a personal question and I know a lot of my friends that’ll be listening are curious about as well, what if anything, can a 30 year old male like myself do to slow down aging? Is it even worth the trying right now and just waiting until stuff like what you guys are working on comes out?

Mike (01:28:42):
No, I just got, we just give the, the common wisdom on that, uh, you know, don’t smoke, you know, reasonable exercise regimen, moderation in all things very diet. I wouldn’t, um, I don’t want to provide medical advice, but I, I’m not a real fan. Uh, a lot of people are really down in a lot of supplements. I mean, I know some people would take two or 300 different supplements a day. I’m in this field, I, you know, study it. Never waking hour. I don’t have the confidence. I mean, a few of these are, you know, you mentioned NAD and so on, or a few of these I’m quite comfortable with, but most of these supplements, we really don’t know that much about. I remember years ago, you know, the free radical theory of aging was the most popular theory of aging and people were swallowing massive amounts of vitamin E for instance. We now know that could have been detrimental. So, um, I would argue a healthy lifestyle, varied diet, keep trim down, don’t smoke, and then wait for technologies that are really gonna make a difference by targeting the clockwork mechanisms of aging itself at most, as you pointed out, based on animal data that we could hope to add a couple of years to your life by such means anyway, and the risk of harming yourself through some, uh, some of these supplements. That’s an unknown variable and oftentimes the unknown can come back and bite you.

James (01:30:22):
What about the injection of STEM cells?

Mike (01:30:24):
Well, no, I’m glad you brought that up and maybe more candid here than is comfortable for me. When all of the science was coming about and president Bush was talking to her country and everything and this aging thing was mentioned, the quack medicine came out in droves. And without naming any company, if you see or hear that there’s a STEM cell therapy available today, come get them. Now, in my experience, and in my opinion, the vast majority of those programs, companies, whatever they may be, are not based on evidence based medicine, meaning there’s no science behind it. So you know, if you’re willing to ante up the money, although give you cells, they call STEM cells. And um, and all of them that I looked at, again, I’m not making a judgment on any particular person or any company out there, but they’re, all of them I looked at had absolutely the ones that I’ve looked at make clear, have absolutely no science behind them. And in my opinion, they require medicine. So I would urge people that say, wow, that STEM cell thing, it’s really big. It’s very powerful. And you see ads in newspapers, please be careful because there’s people out there who will take your money and they really don’t care about the longterm consequences to your health.

James (01:31:56):
And do you have advice for somebody maybe shopping for these types of treatments on maybe quack flags, something that they can kind of a red flag that will deter them?

Mike (01:32:10):
Yeah, there are some, I don’t have them handy. Maybe you could look them up and put them up on your website. It remind me, I’ll send some to you by email. You could put on your website, there are some resources. The national institutes of health has put up some information. There’s some various resources out there to try to help people. But bottom line is the average person out there should know that 99% probably of groups that are reaching out in advertising are probably offering up unproven therapies that are not approved by FDA. So they’re just, they’re skirting FDA regulations and uh, offering up unproven and potentially unsafe therapies. And it’s primarily driven by a desire for them to make money rather than actually help the patients. Sounds a little brutal. A little brutal, but it has to be said because it’s in my opinion, a that’s the state of the play at the moment.

James (01:33:13):
Well that it’s a feeling I’ve had when it comes to STEM cells and I kind of just wanted to verify it with you, so that’s some invaluable information.

Mike (01:33:22):
But yeah, please be careful. The first cells ever isolated, sorry, potent cells that started all this excitement. We’re called H one H meaning human one meaning the first line ever made, the first clinical trial was for spinal cord injury and those cells are still after now over 10 years are still in clinical trials and are still not pre-sale. So when all of these groups are out saying, yeah, we’ve got them now, buyer beware. Please.

James (01:33:53):
Mike, thank you so much for joining me today. I know you’re such a busy guy and this conversation honestly blew my mind. I think it’s going to blow a lot of people’s minds.

Mike (01:34:02):
I’ve enjoyed it. Yeah, long life and pace and long life to all your listeners, and please be safe now and the age of coronavirus

James:
if you got this far, I just want to say thank you so much for listening. If this was all interesting to you, I’d love to connect on Instagram and hear your feedback. I’ll also be posting clips from the latest episodes as well as anything else I find interesting about the biotech industry. You can find me on Instagram at simple biotech, and if you’re interested in the companies that I’m looking at and the companies that I’m excited about, connect with me on angel list at angel.co/jamesruhle. That’s James R. U. H. L. E. thank you so much and be safe out there.