Health Longevity Secrets

The 91-Year-Old Physicist Betting His Body on Mitochondrial Transplant | John Cramer PhD

• Robert Lufkin MD • Episode 263

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0:00 | 58:34

What if aging isn't a hundred separate problems but a single one — an energy crisis inside the tiny power plants of every cell? At 91, Dr. John G. Cramer is betting his own body on the answer.

In this episode of Health Longevity Secrets, Robert Lufkin MD sits down with Dr. John G. Cramer — Emeritus Professor of Physics at the University of Washington and author of "How to Live Much Longer" — the oldest human on Earth to receive an experimental mitochondrial transplant. They unpack a unifying theory of aging built around damaged mitochondrial DNA, why replication errors (not just free radicals) drive most of the damage, and what it felt like to receive escalating doses of "Mitlets" — liposomes carrying fresh mitochondria harvested from young blood platelets — at a Texas right-to-try clinic.

Buy Dr. Cramer's book "How to Live Much Longer": https://www.amazon.com/How-Live-Much-Longer-Cramer/dp/B0DV3ZW5T6
Cramer & Benson white paper (CBC): https://faculty.washington.edu/jcramer/Bio/CBC.pdf
Mitrix Bio: https://mitrix.bio/

CHAPTERS

00:00 Cold open — "the oldest young human on the planet"
 01:18 Meet Dr. John Cramer: physicist turned longevity pioneer at 91
 03:45 Why a physicist became obsessed with aging
 06:20 The unifying theory: aging as mitochondrial DNA damage
 09:40 The 16,569 base pairs that run your life
 13:05 Replication errors vs. free radicals — correcting Denham Harman
 16:30 The damage doubling time: 12 years, then 3-4
 19:50 David Sinclair's information theory of aging
 23:15 James McCully and the birth of mitochondrial transplantation
 27:00 "No negative results, only spectacular successes"
 30:25 Mitrix Bio, Tom Benson, and the Mitlet platform
 34:10 Inside Cramer's four Texas right-to-try sessions
 38:30 Arm injection, belly fat, and the IV mainline that worked
 42:15 What it actually feels like to receive young mitochondria
 45:40 Haplogroup H2A1G1 and the Norwegian great-grandmother
 48:20 The economics: scaling Mitlets to the world
 51:05 Becoming the oldest young human — target age 129
 54:30 What Cramer wants you to do tomorrow morning
 57:00 Final reflections and where to find the book

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The Cellular Time Bomb

SPEAKER_04

Uh that's the Paustian bargain we made. We uh uh we started by uh started as in as a group of immortal cells that we could just reproduce by dividing, and we ended up having this little ticking time bomb built into our built into our cells. Uh where uh when we're young we have lots and lots of energy and we can do all kinds of good things. But as the as time passes, the uh source of that energy begins to diminish and get worse and worse and worse until then your body is compensating for that by doing all kinds of shutdown processes that uh we call the hallmarks of aging.

SPEAKER_00

Umgevity secrets show, where we push the limits of human potential and unlock the secrets to our health and longevity with your host, Dr. Robert Lovkin.

SPEAKER_01

What if aging isn't a hundred separate problems, but a single one? An energy crisis inside the tiny power plants of every cell. Today's guest is Dr. John Kramer, a 91-year-old emeritus physics professor from the University of Washington and the author of How to Live Much Longer. He's also the oldest human being on Earth to receive an experimental mitochondrial transplant. And he's vetting his own body that this is the lifting key to age reversal. Stick around for some great tips.

SPEAKER_00

And now, please enjoy this week's episode.

SPEAKER_01

Here we go.

SPEAKER_04

Hey John, welcome to the program. Well, thank you very much for inviting me, Rob. I really appreciate it.

SPEAKER_01

This is so exciting to talk about your new book uh on longevity and it with focus on mitochondria, and also talk about your experience as one of the one of the one of the earliest, one of the first uh human subjects for to undergo mitochondrial uh transplantation. Uh so I can't wait to dive into that. I mean, first your your background, you spent, you know, what six decades as a nuclear and particle physicist at the University of Washington colliding gold nuclei at Brookhaven and CERN to create the first to recreate the first microseconds of the Big Bang. So what pulled a 90-plus year old physicist into the met wet messy world of mitochondrial biology and aging research?

Why Aging Theories Don’t Agree

From Free Radicals To Mitochondria

SPEAKER_04

Well, okay, I I uh formerly retired from my teaching, uh tenured teaching faculty position at the University of Washington in 2010 when I was 75 years old. And uh so this gave me a lot of extra time because I wasn't the main thing it stopped was my my teaching activities. It didn't stop my research activities. I was continuing to do that for another five or ten years, but it stopped it, and so I had some extra time on my hands, and I was getting older and older, of course, and I began to get interested in the quest and the question of just what is human aging and how does it work and what are the driving mechanisms and is there any way to fix it? Uh that thinking of it as a physicist, there has I have a very mechanistic view of the way the human body works, and I I think it it really has there has to be a cause and there have to have to be treatments. And so I began looking into it and reading the literature. And as a physicist, it's really hard to read the biological literature because they have all of these uh uh things like um uh when they they talk about some protein being produced, they say it's expressed. You know, that that's that's sort of alien language to me. I didn't for a long time understand exactly what protein expression even means. It sounds like the look on its face or or something like that. And so um anyway, I I I took a lot, it took me a long time to sort of learn the biolingo. There there really ought to be uh uh some kind of translation procedure for letting ordinary people learn how to talk biology, but uh there isn't. So I had to learn it by trial and error. And and so I began to read and try to understand what aging is, and what I discovered was that nobody knows that there are like 15 different ideas about what human aging is, and they guys these guys are all talking about arguing with one another and defending their own ideas and challenging other people's ideas, and the whole business is sort of chaotic. And so um this looked very strange to me, and so I began sort of looking into what I could deduce from all the literature, and I learned about telomere length the idea that uh as every every time a cell reproduces, uh uh the little ends of its um DNA get shorter, and after a while they get so short that the process doesn't work anymore, and so there's a there's something called the hay flick limit to cell division, and that looks sort of like a countdown timer that was limiting human age right there. But uh looking at it further, there there was there's research done where uh they, for example, developed a strain of mice that have the telamrace uh produced a lot in their in their gene structure by because of genetic engineering, and it didn't make the mice live any longer, it just made them get cancer more likely, uh more sooner. So uh I sort of got and walked away from that. And then there was the idea that uh your body develops senescent cells. These are sort of cells that have been damaged and were no longer producing their proper function, but for some reason the immune system keeps them from uh being destroyed, and so they just sort of sit there retired in place, and as they do, they generate nasty uh proteins uh called SASP that can cause their neighboring cells to go senescent, also. And again, this looks like like sort of a uh accumulation problem that you're building up more and more of these, and maybe human aging is a result of that kind of thing. And but looking into it further, uh that didn't that seemed to be a downstream effect of what was going on, not the real uh source of the problem. And so I've looked further. And uh I can't and of course then there's then there's a this very exciting work on epigenetic reprogramming where uh the uh uh at 91 years old I have the exactly the same nuclear DNA that I had when I was uh 20 years old. So how how does my body know that I'm 90 years old and not 20 years old? And the answer is that different proteins are being produced uh uh uh in my 90-year-old body than were in my 20-year-old body. And uh the way that these uh protein expressions are switched on and off is by attaching little methyl radicals to a certain part of the the genome that signals that if you're if there's a bunch of these meth methylation uh events that happen, that it switches off the gene and causes it to stop repro stop making proteins and so forth, and it gets wrapped up in a histone and sort of gets it put into cold storage rather than being out there active where it can produce things. And there are ways of changing there are it's been discovered that there are ways of changing that program protein and switching certain proteins off certain proteins off on. And so so again, this looked a lot like uh something that would cause aging because you could sort of command uh a cell to be an old cell or young cell by having its epigenetic programming produced in the right way. But again, looking at it carefully, it looked like a downstream effect, looked like something else was causing this to happen. And then I and then I came to mitochondria. Now, the idea that mitochondria are associated with aging is uh is not a very recent idea. It's been around for a long time. There was a guy named uh um Denim Harmon uh who in the late 1950s uh produced the um um what do you call it? The rat the free radical theory of aging, which which the idea that there's a bunch of oxidizing radicals called ROS floating around in your bloodstream, and that these damage uh do do progressive damage uh and cause uh the cells to be uh sort of uh damaged in a way that that uh leads them into aging. And then when uh this was in the I think 1956 he first published this when he was at Berkeley, and then uh in 1972, after he'd become a professor at the University of Nebraska, he published the mitochondrial uh free radical theory of aging, which was that uh the real uh targets of this damage process are the mitochondria in your cell, which are produ uh producing uh energy. Uh there had been uh some a lot of research in the interim, and he began to realize that mitochondria were the interesting thing. Well, the problem is he sort of got it wrong because he was assuming that damaged mitochondria produce uh this RO this damaging ROS stuff, and the ROS stuff damages the mitochondria, so it's a feedback loop and it goes around and around and around. Um and uh the the whole i idea of the free radical theory uh produced a lot of um uh supplements that uh the antioxidant supplements had created a whole industry in the in the supplement industry. But it turns out that when they studied it, they realized that Harman had greatly overestimated the amount of uh damage that uh ROS does to mitochondria, and that uh if you uh give people a lot of antioxidants, it doesn't really do much. And and and uh and so that uh that theory sort of dampened, and it was uh it was even made even worse by a guy uh uh named Alex Comfort. Uh Alex Comfort became famous in the 1970s for 1972 for writing a book called The Joy of Sex. And uh in and then a bit later he wrote another book in which he condemned the free radical theory of age, uh mitochondrial free radically of aging, because it became known that mitochondrial DNA was being continually reproduced over and over again as fast as the cells could do it, and that there was a process called mitochondrial fission, where mitochondria breaks into two pieces and produces two new ones, and this goes on over and over again on a few-week cycle. And so there was a very active process for restoring your mitochondria. And Comfort Adam argued that this therefore couldn't possibly be the root cause of aging because the mitochondria were well protected and and and in the and there was this active reproduction cycle which was going on all the all the time, which uh should have prevented any of the kind of damage Harmon was worrying about from actually being there. Um that turns out to be wrong. Uh the um what what he didn't realize was that the mitochondrial damage builds up exponentially while the damage from oxidation and whatever else is going on builds up linearly, and so an exponential can always outrun a linear function, and so that's why uh that's why we age, and that's why we're here uh in in our present situation. And so uh, but anyway, the the Alex Comfort efforts sort of uh dampened the enthusiasm for this mitochondrial free radical theory of aging, and people sort of put it aside because it because it had been refuted uh so so to speak by by the comfort paper. So the idea sort of died. But anyway, I got more and more interested in mitochondria because it looked to me like they were the root cause of what's what was going on because they they get damaged, they could it creates an energy crisis. And for example, what's what's going on in epigenetic programming when you when you get older is that the body is trying to deal with this energy uh shortage by putting as much energy as possible into your brain and your heart, which are the sort of really key essential items that need to be protected, and at the in the process it's shutting down a whole lot of other things that are using energy in order to keep the energy balanced in such a way that your brain and your heart are preserved. And so we, in my view at least, we age because uh the body is uh dealing with the energy shortage caused by the sort of progressive damage to mitochondria. So uh then I discovered that there was a company called Mitrix who is uh actively pursuing the kind of therapy that deals with the specific problem I was worrying about, namely mitochondrial damage. And uh that and so I uh contacted uh by by email, I contacted Tom Benson, the CEO, and said, Hey, I'm uh I'd like to volunteer for your program. And and uh it turns out that I'm the I'm the oldest. They have a they have a spectrum of volunteers that Tom likes to call the mitonauts. And I'm at 91 years old, I'm the oldest of the mitonauts, and so uh I uh and so I've recently been going doing some preliminary testing of their mitochondrial transplant transplantation procedures.

Hallmarks Of Aging Through Energy Lens

SPEAKER_01

Um great. Well, I want to I want to dive into all of that. It's so interesting. The book is called How to Live Much Longer, and I have to say it's one, it's really the best book on longevity that I've read. So it's oh there it is. Okay. Uh uh it's on Amazon, independent bookstores, Barnes and Noble, the usual places. But uh yeah, it's it's a great book. And the so the central thesis of the book, as you say, is that aging is fundamentally a cellular energy crisis driven by mitochondrial DNA damage. So why do you believe that the the dozen or so hallmarks of aging that that the longevity field has catalogued and is pursuing so vigorously are all really downstream consequences of this one root cause rather than an independent phenomenon?

SPEAKER_04

Well, I mean there are certainly other things going on besides besides mitochondrial damage, but um uh as I said, uh if you examine each of the, I mean okay, first of all, there are these guys, I can't remember their names, who publ published the nine hallmarks of aging about uh about 2000, and then uh people whose whose uh pet projects were left out became complaining, and so this became the 12 hallmarks of aging in another paper, and then other people were uh were feeling left out, and so this became became the I don't know the 24 hallmarks of aging or the 27 hallmarks of aging or something. Anyway, these are all things that happen when you age. And um the uh the this sort of approach I must must say bothered me, bothered me a bit. There's a famous physicist named Ernest Rutherford, the guy who discovered the atomic nucleus, and he has uh reported to have said all science can be divided into what is physics and what is stamp collecting. And uh and this this is a very very offensive statement to uh people who are not physicists, of course. But but the the if you look carefully at what goes on in biological research, for example, you find that a lot of it is what Brotherford would probably call stamp collecting, because you basically do something, something happens, and you write it up and publish it. And so you have put a stamp in the catalog, so to speak, but you haven't uh carefully analyzed the process in order to understand what the root cause was, uh what the mechanisms were between this the cause and the effect, what the energy balance was that that happened, and so forth. And it I found it very disturbing in reading the literature that the uh when they when people talk about biological processes, they almost never talk about how much energy it costs to do these things. And so if you go back and examine the hallmarks of aging and see what's what's happening when various things fail, uh almost always this is a process that that should be using up a lot of energy until it gets shut down. And so my feeling is that that you can really go down the line explaining one aspect of the hallmarks of aging after another by saying there's an energy shortage, this process was energy consuming, and so therefore it got shut down, and therefore this particular good good thing that the body was doing stopped happening because there's not enough energy to support it, and the the body is desperately trying to keep the brain and the heart going at the expense of a lot of other things which are considered good but secondary. And uh, so uh it all makes a lot of sense if you look at it from the point of view of energy. And as a physicist, I learned a long time ago that track following the energy is sort of like following the the money and watergate, uh, that uh that the energy sort of goes through everything, and if you don't have enough energy to do something, it doesn't happen.

The Faustian Bargain Of Mitochondria

SPEAKER_01

Um yeah, yeah, I I love that. Well, so well, speaking of energy, you have a particularly poetic uh passage in the book where you describe what happened uh roughly two billion years ago when one of our ancestor cells began transitioned to become multicellular and engulfed a bacterium and got abundant uh ATP, and you describe it as a Faustian bargain that traded cellular immortality for energy. So maybe unpack that trade for our audience. So, why did gaining mitochondria mean we had to start aging?

mtDNA Replication Errors And Exponential Damage

How Eggs Select Young Mitochondria

Ethics Barriers And Right To Try

Haplogroups And Mitochondrial Mismatch Risk

SPEAKER_04

Well, let's let's go back to the fact if you go back back and back and back, you can find some of our cellular cellular ancestors, which were single-cell creatures. And as single cell creatures, they reproduce by dividing. And so they divide and divide and divide, and they never and they never get old because uh they're they're they're essentially immortal, but but they're only a single cell. And so that there's a certain that's a price of immortality that probably one doesn't want to pay by just being a single cell. So and and and uh this was on the uh in the oceans of the earth when something something disastrous was happening, namely some of the bacteria had figured a way. I mean, there was all this sunlight coming in from the sun and the energy was sort of going to waste. And a few of the cleverer bacteria figured a way of doing photosynthesis so that rather than uh consuming the hydrogen that was present in the uh in the Earth's atmosphere at the time, uh, they could uh take sunlight and uh and glucose and make ATP energy that way. And the problem was that the waste product of this process was oxygen. And so as they produced all of this, did all of this photosynthesis in the ocean and became one of the most dominant organisms in the whole world, uh they were polluting the atmosphere by filling it with oxygen or by putting it uh in oxygen, and the hydrogen was getting oxidized and going away. And so uh some of the more advanced cells in the uh our one of the one of the more advanced cells, our ancestor, a uricroat, um, was still breathing hydrogen and it was suffering badly because the hydrogen was going away and its supply of energy was very limited. And along came a little bacterium that was uh was oxygen breathing. The bacteria, some of the bacteria had figured a way of breathing the oxygen by then, and it gobbled up this little bacterium, and instead of uh eating it and taking it apart and using its uh processes, it it uh re- achieved a symbiosis with it, where it allowed it to reproduce and live inside the cell and in the and provide it with it with as much oxygen as it wanted. And in exchange, the little bacterium went into high gear and started cranking out uh as much ATP based energy as as possible. And uh this uh this gave the this made the this eukaryotic cell into a into a supercell that suddenly had many, many orders of magnitude more energy available than it had had. previously it became uh sort of the dominant uh life form in the in the earth's ocean and and took over and the um uh the the um uh uh the explosion of multi-cell animals that had happened a while later was driven by all this energy that this uh symbiosis between uh a energy an energy producing bacterium and a uh hydrogen breathing uh a previously hydrogen breathing uh cell could could could produce and uh but the there was a there's a problem with this and that is that the the parent cell uh the the eukaryote that ate the the the mitochondria bacterium uh was uh had very carefully protected DNA the DNA was in a cell nucleus uh uh all of the DNA was wound up in little histones and carefully protected by the um by repair neck mechanisms and by uh uh the immune system and it it it was very effective and it had very effective repair mechanisms for fixing any problems that happened to go come along and so therefore it's it's it's my its uh nuclear DNA was very carefully protected. The bacterium on the other hand uh reproduce re very fast and and uh they don't really worry that much about how how careful carefully their DNA is protected they have a little exposed ring of of DNA uh the nuclear DNA has uh has telomeres on the at the end it has it has epigenetic programming uh it has uh introns and careful and all kinds of stuff like that and it has very effective repair mechanisms the bacterial DNA has none of that it's just a little little 16569 uh uh base pair ring that's out there well I guess it's it's it's sometimes coiled up but other than that it's it's just out there all the time and all the genes are turned on all the time there's no epigenetics to turn on some of them and some turn off some and so it gets damaged and and and it turns out that if you carefully examine what damages this little ring of of uh DNA that the the mitochondria have it's mainly uh replication errors that there's an enzyme that goes down the down the DNA making a new copy of it and once in a while it makes a mistake it has certain proofreading capabilities but they're not good enough and so uh it it makes three different kinds of uh of mutations in the in this process the the the raw stuff that uh Harman was worrying about represents about 15% of the mitochondrial DNA damage this uh this uh replication problem represents almost all of the damage and it it has to do with with substituting one base pair for another in one place or another called a point mutation and there are two kinds of the of those point mutations whether you put the complementary uh uh uh uh uh base pair in for the base pair that's removed or whether you put the same uh same type of base pair in that was that is the one that's removed or else do you just leave out a a few thousand uh base pairs and make a deletion mutation where you have a ring that's uh that's smaller and the the the problem with those deletion mutations which are which are produced a lot in this uh replication process is that they're shorter that you have the ring instead of being 16,569 pairs it's it has 15 or 20 percent of its of its DNA missing and of course that leaves out some important uh gene instructions about how what's supposed to happen but what also happens is that the replication process can reproduce those little uh smaller rings faster than it can reproduce the others and so the uh the the damaged uh deletion mutated DNA have a replication advantage they out can outrun the other guys and this leads to an exponential rise in the uh in the in those damage mutations you if you have a population that has some of these and some of the others the fraction of the uh of the of the ones with the deletion mutation will grow exponentially and uh that's the uh that's what's happening to um and and not only does it there's a uh there's a German paper that w where they studied this in detail using sequencing and what they found was that when you get to be about age 65 suddenly the slope of this exponential changes and reproduces more fac rapidly it instead of having a a doubling time of about 12 years it has a doubling time of three or four years and so uh there's probably no accident that 65 is the sort of canonical retirement age of human beings because uh that's the time when suddenly your mitochondrial DNA uh begins to to decay exponentially at a much rapid much more rapid rate and so um the the reason for that we don't know but it's probably because uh the uh the uh uh mitophagy that goes around uh checking mitochondria mitochondria and making sure that they're working and calling the hit squad for the ones that are failing uh requires energy and when the energy gets to be below a certain level the mitophagy falls off and then and the and and and things go from bad to worse. So anyhow uh that's the Paustian bargain we made. We uh uh we started by uh started as in as a group of immortal cells that could just reproduce by dividing and we ended up having this little ticking time bomb built into our b built into our cells uh where uh when we're young we have lots and lots of energy and we can do all kinds of good things but as the as time passes the uh source of that energy begins to to dimin diminish and get worse and worse and worse until by the time you get to be my age uh your might your mitochondria have a large fract a large fraction of your mitochondria are damaged maybe 15 or 20 percent of them and uh and you're not and you have an energy shortage and your body is compensating for that by doing all kinds of shutdown processes that uh we call the hallmarks of aging. Yeah I mean that's a that's a great great discussion and of course it begs the question that uh you know during uh you know 40-year-old parents have a 40-year-old embryo which epigenetically rewinds through uh uh dedifferentiation and uh rejuvenation to a pluripotent embryonic uh stem cell eventually what is the analogous mechanism to to basically select healthy mitochondria because there is no epigenome obviously and what would do is that well understood about a funnel function yeah the the in the female reproductive process there there's some very special prop things that go on at certain times um there's a winnow what's called a winnowing process in my book there's an appendix that goes into great detail about what the winnowing process actually involves but basically what's what it what it is is that the the body does not want to produce a baby that has old mitochondria in it and so uh what happens is that uh the there is a process that carefully examines all the mitochondria in a mother in a mother's egg cells and selects out six or eight of them that are uh are are found to be robust in that they're in that they uh do their oxygen metabolism is really high and they they uh show no evidence of any any other problems uh as far as the inspection enzymes are concerned and they're all segregated in into one location in the in the egg cell uh and um then uh a lot of the other egg cells that have bad mitochondria are killed off and the and the one that has that has the good mitochondria become comes in action and so and that those six or eight mitochondria then get reproduced uh uh very rapidly to become um oh I think it reaches almost a million mitochondria uh in one cell at at a certain point and uh and then it gets segregated divided out and divided out and divided out until uh into into the embryo but anyway that that's how our mitochondria rejuvenated that there's a selection process that that selects out only those that are very robust and producing a lot of energy metabolism as the progenitors of all the other mitochondria in the body unfortunately once in a while one of the bad mitochondria sneaks into this six or eight uh select group and the result is it gets reproduced exponentially as well and uh and and and we have children with genetic damage because their mitochondria have missing pieces or point mutations or something like that that manage to creep in with one or two bad mitochondria getting in with the good ones and um one of the things that we could in principle do with um um mitochondrial transplantation one of the probably the one of the earliest uses will be to treat these children that have have bad mitochondria by giving them a new supply of mitochondria that don't have that kind of damage. And that's actively going on but uh there are ethical barriers to uh doing things like that and so a a lot of hospitals who in principle could be treating children like that right now are banned by their ethics board from actually moving forward so uh it's nasty nasty situation which in principle could be uh treated a lot better than it that it is at present because of uh people people are being uh utterly cautious um I you know I'm I'm 91 years old I don't have time to wait around for ethics boards to worry for 10 or 20 years before approving some treatment so uh I um we're we're going to states where they have right to try laws in order to uh investigate uh do the investigations that we're doing um yeah and congratulate applaud you for stepping up and uh and doing this it's it's really great. I mean speaking speaking of transplantation mitochondria as you say are famously inherited only from the mother that's the mitochondrial mother hypothesis and all that once in a while a mitochondria from a sperm sneaks in but it's that's a very rare process rare rarely yeah and in your book you discuss the the haplogroup matching problem in other words that not all donor mitochondria may play nicely with everyone's nuclear DNA so how worried should we be about mitochondrial mismatch and is autologous transplantation the obvious answer or does it defeat the purpose and maybe you could talk about your uh your your particular procedure yeah I okay yeah let me uh let me explain about mitochondria uh one of the there there's a pro a um uh enterprise called genetic genealogy where you can uh for a hundred dollars or so you can have your uh your DNA and your mitochondrial DNA analyzed and they will tell you uh how your DNA and your mitochondrial DNA differ uh uh from other people and you can use this to find your own relatives and you can track your mother and grandmother and great grandmother and so forth. My mitochondrial DNA came from my Norwegian great grandmother who came from from Norway and she passed it on to my grandmother and my my uh mother and to me and uh I have haplogroup that they they divide the they care characterize mitochondrial DNA in terms of this the of these mutation structures uh into what are called haplogroups and there's about 20 or 30 of them. It sort of depends on how far how picky you want to be but but my mitochondrial haplogroup is H2A1g1 and that means that I that I am uh I don't know I have like 40 or 50 mutations different from the mitochondrial Eve that you can track back to that that uh started this process a long time ago. But the one of the things that we see in mitochondria is that mitochondria can be either optimized to produce as much energy as possible or as much body heat as possible. And people who uh evolved in the northern climes uh probably are are more interesting are uh probably the body heat business is a big big advantage they can stay warm in cold weather warmer in cold weather and so their mitochondria are probably optimized that way uh people that grew up in in Africa or people who evolved in Africa and so forth probably the having extra body heat is not exactly where you want to be and whereas you'd like to have more energy and so their mitochondria are optimized in the other direction. Those are two examples of how the hop haplogroups steer things around we don't understand a lot about what exactly the uh the haplogroup structure is is uh is demanding but uh that's certainly one of them and there and there are a few others that people talk about anyway the point is that your mitochondria and your nuclear mitochondrial DNA and your nuclear DNA work together uh uh it used to be when the when that bacterium was first captured that we were talking about that all of its DNA all of its um all of the programming for producing a new one was encoded in its DNA but over the next two billion years um the uh the mitochondrial genes are uh out there getting damaged and the nuclear genes are protected by and and and are have a damage rate of about 20 times smaller and so uh a lot of the mitochondrial genes move to the nuclear DNA leaving only 13 of them behind uh our mitochondria only have 13 genes that and that are involved in making new mitochondria and these are ones that produce what are called uh hydrophobic proteins uh hydrophobic protein doesn't like to be in water and if you put it in water it sort of balls up and folds itself up into a little the tightest little ball possible and then when it gets where you want to use the protein it has the wrong shape and so it doesn't work very well and so the um mitochondrium so the mitochondrial genes are uh are that didn't move probably didn't move because they make hydrophobic hydrophobic proteins anyway those are the ones that are getting damaged those are the ones that uh are causing us to age those are the ones that uh kids who have genetic damage uh have have those have those proteins coming out of the wrong form or else not at all and so uh so the the question is if you uh receive mitochondria from some random donor and and I might point out that mitochondrial transplantation is not really all that new anytime somebody gets a blood transfusion or a stem cell treatment or a plasma replacement treatment they're getting millions and millions and billions of mitochondria in that process uh and the and while they are very careful about checking blood types before you're doing a blood transfusion they do not check the haplogroup and so therefore you're getting uh haplo transplantation from somebody uh somebody at random who may have a very different mitochondrial haplogroup than you do and the the the the little mitochondrial gene may be qualitatively different um and so uh but the pro point is that uh the the kind of the amount of mitochondria you get from such processes are not uh not enough to sort of dominate the your mitochondrial structure they represent they might get as much as you might represent as much as a few percent of your mitochondria but they're they're not going to dominate it. And so the question is if you but if you go to a really big trans transplantation where you're transplanting 15 or 20 percent of your uh providing the body with 15 or 20 percent or more of new mitochondria uh what does that do? And and let me also say that there's probably a multiplication factor that if you have an energy uh your body is uh if if it's in the process if an an older individual uh having this energy charge we're talking about probably has uh a uh body is probably commanding the cells to make more mitochondria but the cells if they don't have enough energy can't respond so if you do a mitochondrial transplant that produces a lot of new energy that that probably causes your body to go into and into a more much more effective mitochondrial reproduction process which will give you more mitochondria as a secondary effect of of producing it so putting in one new mitochondria might make three or four extra mitochondria in your body so there there there there we expect there to be some kind of of a doubling or tripling processing going on when when when you do the transplantation but anyway getting back to what I was saying if you if you put in random mitochondria we don't really know what happens uh there have been experiments on my on mice and rats where they gave uh a a given subject half one kind of mitochondria and half another kind of mitochondria to see what happened and these animals are definitely not as healthy as their as their uh cohort as the cohort that has only one kind of mitochondria in them so that there are some secondary health problems that seem to be creeping in but how how serious this is we don't know it it may be a serious problem that we have to worry about. It may be something we can neglect um there may be kinds of mitochondria which might might might are like typo blood we might call them hot typo mitochondria that you could use for universal transplants because they're not going to do anybody any harm but uh the the research hasn't progressed enough so that we can really answer this question and know whether such things exist or not yet but I'm I'm sure we'll find out uh when we when we get around to it but we're not we're not there yet. So um anyway the to be on the safe side you'd like to have your new mitochondria have exactly the same genetic profile as your old mitochondria. But uh uh and uh there there are ways of doing this but they're fairly expensive. There there may be cheaper ways of providing uh somebody with a mitochondrial transplant where the uh where there there's only a partial or an or a haplogroup match or no haplogroup match at all. And so um that this is something that's gonna have to be worked out by the medical community as as the process continues. Clearly in the emergency room you're not going to worry too much about mitochondrial uh about haplogroup matching you're because you're trying to save somebody's life but um in if if you're trying to make somebody's life better by by by uh doing some kind of rejuvenation like thing using mitochondria that then you begin to worry about whether uh you're not supposed to do any harm in medicine and so the question is is are you doing any harm by by having a mitochondrial mismatch?

Emergency Uses And Rejuvenation Sequence

SPEAKER_01

And that's a question for research we don't know the answer yet but uh it since we don't know the answer it's probably better to be on the safe side and reproduce your own mitochondria rather than taking in taking in somebody else's um yeah I mean and and since you this we're talking today kind of about longevity and aging effects of mitochondria but in your book you talk about and you just alluded to emergency rooms where one can imagine a scenario where the person comes in with an acute heart attack or uh trauma, brain stroke uh sepsis where mitochondrial infusion with the energy benefits could be beneficial there.

SPEAKER_04

And there's even one prospective control trial for intracardiac injection of uh platelet derived mitochondria transplants uh uh than more than there've been more than that actually though um um uh McCauley who was the pioneer in this air area says there have there's no area where they have transplanted mitochondria for a particular organ that hasn't been a spectacular success. Uh that it it if so far they've never had a negative when they've done a mitochondrial transplant to fix something it always gets fixed somehow.

SPEAKER_01

Isn't that interesting well it it speaks to being a root cause for for Any of these conditions that energy deficit is a is a universal uh pathology uh below many of these other diseases.

SPEAKER_04

Yes, um particularly when when you're old. Um and so the question is well, if you're running out of energy, then the first thing you want to do is fill the gas tank but there may uh uh on your vehicle, but but maybe uh and so that you have lots of energy, but there may be other problems that need to be dealt with too. And probably anything else you want to do requires energy. And so um mitochondrial transplant is the transplantation will be the first step you want to do in rejuvenation, but it may not be the last step. We don't uh the question is okay, the body has let let us assume that this model is correct and that the body has progressively shut down various repair and uh and maintenance processes that require a lot of energy because the energy supply is getting limited. If you then change this situation by adding a lot of new energy, what happens? Does the do the do these processes that get shut down automatically come back online, which would be wonderful if it was true, or do they stay off because uh the there's no mechanism, the body doesn't have a mechanism for uh for reversing what it what it did. We don't know. Um and so uh the first thing to do is to provide the energy and see what happens. And if it doesn't happen, then we may have to go in and make the telomeres longer, we may need to go in and cause the senescent cells to go to clear out the senescent cells, we may need to go in and do some of the some of this epigenetic reprogramming that people are seem to be so excited about. But uh it may not be necessary because it may be that the body takes care of those sort of things when it has enough energy to do that. And so um uh that that's a question we would really like to know the answer to, but we'll we'll we should be prepared to have to do other things if the my if mitochondrial transplantation doesn't do the do the whole job of rejuvenation. Um and I am I'm happy to be in the middle of that that that process so that we can learn what's going on.

His Early Mitochondrial Transplant Experience

SPEAKER_01

Well, speaking of that process, I'm sure everyone is very curious about what your personal experience was with these with these procedures. And to be clear, these are very early safety procedures, not going for a high dose, so it's really uh kind of a proof of concept, but maybe you could just speak briefly what it was like and what you experienced, if anything.

SPEAKER_04

Yeah, um the the I've I've done four sessions of mitochondrial transplantation, and uh I I should say that I uh I was originally supposed to do one in early January, and I came down with a bad case of bronchitis, and uh we didn't want to do anything like that at the time when my immune system was uh was up in the air, and so we we put it off for two weeks, and then uh I went to Dallas, uh Dallas Fort Worth area. Uh Texas has it has a right to try uh has right to try legislation that makes it a good place to do these things. I went to the Dallas Fort Worth area and uh over a period of of uh over a relatively short period I got uh four injections of of mitochondrial uh okay, first let me back up a little. Where do you get the mitochondria? You have to have a donor, and the and what you want is the donor's blood platelets. Blood platelets contain about eight mitochondria each. And uh when they get old, they make a little um sort of package, uh a little liposome package, uh call which we can we call a mitelet, which contains the the mitochondria and and and is sort of intended to carry it from the blood platelet which is coming apart to some place where the mitochondria are needed. The body does this automatically. And so uh their Mitrix has developed a procedure for for uh taking platelets and extracting their mitlets uh for injection, and so that was what was done, and they injected me in four different places in my arm with uh with these mitelets from uh from blood platelets, and uh no effect. Uh if I I felt fine the next day. Uh a week later they uh injected, they did it again with ten times as many mitochondria, and they also uh did an injection into my belly fat uh uh with with a fair with an even larger dose to see if that had any effect. No effect at all. Uh then I I I went home and came back uh uh uh about a couple weeks later, and they uh they they did they did it they mainlined me. Uh my phone's ringing, but I'm just gonna ignore them. Um the um they injected the uh the the miteless directly into my bloodstream and uh I f uh I uh after the after this was done uh we went to the art museum and I walked around and I I I felt a bit energized then and I felt uh felt quite a bit more energized the next day. But I I uh there's this placebo effect that you have to be careful about, and so uh reporting that you have you feel good after something happens may have something to do with what what that was done to you, or it may be that uh that your body appreciates the attention, so to speak. And so uh I don't know. But anyway, that was the third time, and the fourth time they injected me, they did another uh uh injection directly into my bloodstream uh with uh about six or eight times as many mitochondria as they had put in in the previous time. So we were we were sort of going up stair steps, going up and up and up uh to higher and higher dose dose levels uh with uh and um uh there were never any negative effects, and uh and I would say that there's subjectively there seem to be some positive effects, although uh I I can't really say that the positive effects were not something having to do with the placebo effects. But anyway, uh but I I I I presently have gone through four of these. I feel very good. Uh I feel very very energetic. I've started a new couple of new writing projects, uh, and uh and I think uh there's no evidence at all of anything bad happening from this level, that level of mitochondrial transplantation. The next level, the next level is to find out whether my aging uh cells actually can be uh reproduced in a aging stem cells can actually be reproduced in a bioreactor, and then if so, uh crank up some bioreactor, make a lot of mitochondria, and try it at a at a higher level. But uh that that's uh it's in the works, but uh it has uh certain funding problems that need to be addressed before it goes very far.

Scaling Up Costs And Five-Year Outlook

SPEAKER_01

Um, you certainly so you're on the you're on the path in the middle of this process, and we'll definitely have you back again to uh to talk more about it. But just looking in a crystal ball, why why would you see this in five years, assuming the funding comes through? Uh what would it look like? Uh what what would this this happen? What is high volume mitochondrial transplantation look like as a procedure? Uh when will it be available for the rest of us?

SPEAKER_04

Yeah, uh the problem is that it costs a lot of money. Uh a bioreactor is a big machine, and you put cells into it, and then you uh it's sort of like a uh like what they do in a brewery, so to speak, with with with uh with yeast cells. Uh and you brew up uh stem cells, then you extract their mitochondria uh and and then you inject them. Uh the the problem is that uh bioreactors are expensive objects and they and there's a lot of uh technical staff that has to be uh keeping them going and so forth and so on. So it's not cheap. And so uh I I I don't I hesitate to c to to name a dollar figure, but it but it's uh going to be something comparable to a heart transplant or something in in terms of the the medical cost of it just because of the amount of of the the complication of it. Um the um uh the then the question which I uh talked about earlier is what what what is the result of a large volume mitochondrial transplantation? Do you does the re does the rejuvenation that you you're sort of shooting for happen immediately, or does it uh or do you have to do other things in order to cause uh get the body's attention and cause it to do the things that that need to be done? And uh uh like I said, we're prepared for either alternative. Uh Mitrix already has a uh uh has um made uh arrangements with companies that are doing these other kinds of of uh of uh rejuvenation efforts to uh coordinate it and and do do them together if necessary. But we don't know whether that's gonna exactly what what's gonna happen because uh I'm the test, I'm the I'm the the lab animal, the guinea pig, the rat, who the lab rat who's uh going to be uh going to be in the middle of this, and we don't really know what's gonna come out. That's why we're doing the experiment. I I'm an experimental physicist, and I well know that you can get surprises when you do experiments, and so uh we'll see.

What Success Looks Like At 129

SPEAKER_01

I love that, and I love that you said in the the the that this work in your in your book might let you become the oldest young human on the planet 30 years from now, you would be the oldest living human ever documented. So, what what does that success actually look like for you personally? And then and also maybe where can listeners follow your trial, get the book, and keep up with what comes next.

SPEAKER_04

Well, okay, yeah, I'm uh I'm as I said, I'm 91 years old. In 30 years, I will be uh 129, I guess. Uh and uh the oldest human being is about 126 at the moment, and so uh uh a woman in England, I believe. And uh so uh let us i if these if this treatment allows me to live another 30 years, then I I uh uh and I am I have a head start on a lot of other people because I'm so I I'm already 91 years old. Uh I I may very well be the oldest person on the planet. Uh on the other hand, um something may go wrong. Uh things do go wrong in medical research, and so one has to be careful, and um or or it may not work at all, and and and uh and father time and mother nature may catch up with me, and so we'll find out. Um but um I uh uh I I still have a I'm still fair fairly productive. I'm I'm I'm working on books. Uh I may even do another science fiction novel, although although I I had so much trouble getting my last one published that I'm I'm not very enthusiastic about getting into into another one. But um you know my uh I wrote a science fiction novel in about 2015 and my editor died, and then the publishing company decided that they didn't want to publish any more hard science fiction, they wanted to focus on uh feminist fantasy, and so they canceled my contract, and I had to spend several years looking around for another book contract, and it got published as an e-book only with no paperback, but no printed version, and which I wasn't too happy about because you can't sign an e-book, and I like signing books.

SPEAKER_01

But uh well, yeah, and well, this this book you don't want to miss, and it is coming out in in ebook, but also in in regular format. It's called How to Live Much Longer. And John, you're an inspiration to us all. We can all we could we can all learn from you, and I I can't recommend this book highly enough. It's it's it's very readable for people who don't know anything about it, but it's it has a lot of technical detail for experts will get a lot out of it also. So it's really uh a novel way to look at aging, I think, through the through the lens of mitochondrial energetics, which uh is so so exciting. So thank you, thank you again, John, for for being on the program.

Subscribe Review And Listener Requests

SPEAKER_04

It's been my pleasure. Yeah, I I I um I had fun writing the book. I hope you have fun reading it.

SPEAKER_01

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SPEAKER_02

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SPEAKER_01

That's good. I think it was good.