Is There a Central Aging Clock with Dr. Sheldon Jordan
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Welcome back to the Health Longevity Secrets Show with your host, Dr. Robert Lufkin. His book titled, Lies I Taught in Medical School, is a New York Times bestseller. See the show notes for a link to download a free chapter. And now, please enjoy this week's episode as we look at the central aging clock in humans with Dr. Sheldon Jordan.

This week, we're broadcasting a fascinating presentation from my good friend, Dr. Shelley Jordan, where he discusses not only the importance of a central aging clock in humans, but also a possible treatment to reset it. In fact, he's even offered the procedure to me. So please let me know if you think I should take him up on the offer.

The presentation is from the most recent Radfest meeting, which is set to take place again in Las Vegas on July 10th through 13th. You really don't want to miss it. This week, we get to unlock the secrets of aging with the intriguing insights that Dr. Shelley Jordan, who's a distinguished neurologist and professor,

We journey through the concept of the, quote, grim reaper clock, exploring how a central brain clock might dictate the course of our lives from puberty to menopause and beyond. Through the thoughtful lens of the grandma hypothesis, we ponder how slow aging could have provided humans an edge in adapting to environmental shifts.

Prepare to challenge what you think you know about aging as we navigate the intricate relationships between age and performance. Why might athletes and intellectuals peak so early? And what role does the hypothalamus and pineal gland play in maintaining our youth?

Learn about the groundbreaking research by Dr. Kai, potentially reversing aging by using exosomes in mice, and explore innovative techniques like genetic reprogramming and ultrasound technology to influence mental health. We consider how transposons might impact age-related diseases and discuss the tantalizing possibilities of controlling the aging process itself.

This episode offers a glimpse into a future where medical science could redefine what it means to grow old. This episode is brought to you by El Nutra, maker of the ProLong fasting mimicking diet. If you'd like to try it, use the link in the show notes for 20% off.

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This scan is available anywhere in the U.S. without a doctor's prescription. See the attached link and use the code LufkinCT for $100 off. Join the health longevity medical imaging revolution today. And now, please enjoy this week's episode.

Who we have next, not what. Well, he's kind of a what. He's a super guy. Dr. Sheldon Jordan is a board-certified neurologist considered a top doctor by the best doctors in America, Who's Who, Global Edition, and Grota B. He is clinical associate professor of neurology at UCLA and USC. He specializes in advanced imaging techniques, interventions for brain and nerve injury,

anti-aging of the brain and regenerative medicine. He does a whole bunch of other stuff but what we want to know is what he's going to tell us about right now. So, oh, you're here. Take the stage. So we will be talking about a technology for growing young and we'll start out with a question. Is there a Grim Reaper clock that determines when you age and when you die? Now,

Why might there be a need for a Grim Reaper clock? Let's think about that. Our story begins in a remote island in the Bering Sea. The story was started in 1944. There was this group of American naval officers that was stationed on this island, St. Matthew's Island, which is around the Arctic Circle during World War II.

and the problem was feeding them while they were there. So someone had the bright idea, let's get some reindeer that will live in that environment, put them on this remote island, and they can be a source of meat for these naval officers. So at the end of the war, the sailors came home and the reindeers stayed on this remote island. And so what happened? Some years later,

Observers came to this island and what did they find? They found there was a drastic overpopulation of reindeer because there are no natural enemies on this island. Fast track a few years later. Observers came back to this island and now what did they find? All the animals were dead. So what's the take-home message here? That when you have no natural predators,

it appears that animals don't die fast enough to allow an ecosystem to keep that species alive. So death may be great for the species, but perhaps not so good for the individual. So what's the evidence that a central clock actually exists in the brain that controls not only the brain, but the entire body's aging process?

So first of all, life milestones appear very much like clockwork. Puberty, menopause, dementia, and even death appear to happen around a predictable age with just a little bit of variation, very clock-like. What's also quite remarkable is the ability of the brain to develop and for people

individuals to grow in a way that they acquire skills in a particular time frame, very regulated. So what part of the brain develops at a certain age and what develops at a later age is very much according to a specific clockwork. And we'll come back to this chart a little bit later. So you might ask, what age is the human clock set to?

And I would now present the grandma hypothesis. So, first of all, aging, if you think of it, is dying slowly. We have this misconception that the Grim Reaper will cut our lives short very quickly. But in most cases, that's not what happens. The Grim Reaper clock does not kill you quickly. It kills you slowly.

by making you age. This mechanism allows for a variable resistance to famine and pestilence. So let's talk about grandma. Grandma is luxury. Times of plenty, we have more children. In fact, we have too many children for one mother to care for. So having grandma around is a nice luxury. Because when it's times of plenty, we have more children,

But at times of famine, times of pestilence, times of strife, we don't have so many children and our children are dying, so we don't need grandma. So the variability of aging slowly and becoming more frail allows for this natural selection to allow our species to exist.

So if you take a natural environment, you look at what was the typical age of people dying in prehistoric times, the life expectancy was really 35 years old. You don't see many old cavemen. And actually, if you look at some phenomena that we're all aware of but never really quite think about, by age 30, an existential freefall starts. Now, what do I mean by that?

fertility drops precipitously. Physical endurance, agility, and recovery drop very quickly. Also, cognitive flexibility and creativity drop. Let me give you some examples. So if you look at a graveyard in Rome for gladiators,

their average age at death was 30. And what that means is, by age 30, you don't have the quickness and the strength and the ability to survive in that environment. And of course, the result of that is, you're dead. Not unlike what happens with NFL players or baseball players, where you pick a sport. When it comes to physical endurance and physical performance, by the time you're in your 30s, you're in the decline.

How about your brain? This is a very interesting fact. Chess masters, so chess, extreme dependence on very advanced thought. It really stresses the human brain to its limits. And you look at who are the chess masters that reign worldwide during the 20s and 30s. You virtually never see them in their 40s or 50s. How about invention? Take someone like Einstein.

Take people like Edison, take Madame Curie. When did they make their great discoveries? It was all when they were young. When they got to be age, beyond age 30, they were just biding their time. Now mice on the other hand, they only live two years. And they can only live two years because they have a lot of progeny. So if you have a lot of offspring, you got to die fast because otherwise there'll be too many individuals of that species overpopulating that ecological niche.

Dogs are sort of intermediate in this. They live 10 to 15 years generally because they have sort of less offspring than mice but more offspring than humans. So how does the clock work? Let's look inside of it. So if you take a human brain, this is mine of course, and we slice into it, we'll see something that is actually relevant to this whole discussion. We'll see the hypothalamus, which is

in color here. And if you take a slice through that histologically, you'll see that it's lined with stem cells around the third ventricle. Now these stem cells produce exosomes. The exosomes have signaling molecules that basically tell the rest of the brain to stay young. When these cells become exhausted, it appears as if a default mode is to grow old.

So these exosomes are released into the third ventricle and they move back and forth between other components of the brain as the blue fluid is showing you. And that keeps the pineal gland healthy and it keeps the rest of the brain stem healthy. When you start losing this type of signaling, it's the early onset of Alzheimer's disease-like changes that you see by age 35.

Now what's happening here? It turns out that the pineal gland, it receives signals from the hypothalamus to keep functioning, but it has a duty cycle which wears out because it calcifies. In the process of making melatonin, among other hormones, it self-destructs. So you get calcification of the pineal gland. It can no longer make melatonin, which is required to keep the hypothalamus young.

So here you can see someone on the right side with that arrow showing just a little bit of calcification in the pineal gland. And on the left side, you see someone with Alzheimer's disease who has dense calcification of the pineal gland. And what's happening, if you look at melatonin production by age, it drops dramatically from age 5 or 10 all the way up through age 70 when you're virtually making no melatonin. And we know that if you do a pinealectomy,

In a sheep model, for example, as in this study, you lose all those stem cells that are required to keep the hypothalamus working in a young format. So if you look at a normal sheep on the left,

You can see all those little black dots are stem cells infiltrating from the third ventricle into the hypothalamus to keep the hypothalamus working in a young fashion. If you cut out the pineal gland, you see what you see on the right is that there's virtually no stem cells that exist. So what happens when you lose hypothalamic function? Well, you stop making hormones and your body starts to wear down, but also you

when the pineal gland stops making melatonin, melatonin turns out to be a key element to keep your thymus and your immune system running in a young, youthful fashion. And when you lose that type of stimulus, you get immunosenescence. And as everybody in this audience will know, immunosenescence and the resulting inflammatory profile that occurs in elderly people is the result, and you start to age.

So, those are the inner workings of the clock. But like any other clock, can we reset it? And can we reset that in humans? So, the first inkling of this possibility came from Dr. Kai's clinical research operation at Albert Einstein. He's someone that I have the privilege of working with. In my humble opinion, I think he's going to win the Nobel Prize for what he found. This is what he did. Those stem cells that line the hypothalamus that we talked about,

he was able to selectively destroy them using an immunological event. So you kill them and the rest of the hypothalamus is left intact. What happens? This young mouse immediately becomes old. Their hair falls out, they get sarcopenia, osteopenia, they become sexually inactive and cognitively impaired. Now think of it. There hasn't been an acceleration in all these environmental factors that we're talking about.

simply that what was done was these lining cells in the hypothalamus were destroyed. Instant aging. That's sort of interesting, but this is the part I really like. You take that same animal and this time you put in a pipette into the hypothalamus and you infuse directly exosomes from a young mouse. What happens? The mouse becomes young. Hair grows in, the muscles become strong,

The bones become strong and they become cognitively normal. Again, we haven't done anything to their diet. We haven't done anything to their exercise. We haven't given them any special supplements. There's no heavy metal intoxication or any of these other things that we all worry about. This is simply resetting the clock. So the big question is, can the aging clock be reset in humans? I would abbreviate this TGY, Technology for Growing Young. This is very easy to do.

We do happen to have the intellectual property of this. However, this can be adapted to any clinic environment. Fairly inexpensive, accessible, and really quite inexpensive. This is what it looks like in a clinic setting. And here are two of my technologists. One is modeling as a patient, and one is modeling...

as a technical person applying this. So you have an optical tracking device at the other end of the room. It's the same device that's used in neurosurgery to find where brain tumors are using the patient's MRI data set to give us the anatomy. That talks with the probe that is being focused in the particular target that we're interested in. Let's say it's the hypothalamic clock in this case. So we can use ultrasound guided in this fashion

based on the patient's own MRI scan data to be extremely precise in stimulating with focused energy, in this case ultrasound energy, to something that's as small as a centimeter or less in size. So let's see how this works. Think of a couple of exosomes that are given intravenously now, and they're floating through the brain in a blood vessel, and then you give an ultrasound focus

to those exosomes, what happens is they adhere to the endothelium because they're receptors that are stimulated by the ultrasonic wave. They get absorbed into the cells lining the vessels. Some of those exosomes are going to be digested like the one on the left. However, the one on the right gets completely through the endothelial cell by trans-cellular migration and ends up in the brain. So the brain journey begins.

Hopefully everybody followed that. So this is an intravenous injection of exosomes. Ultrasound turns on the adhesion molecules only in the target zone. The exosomes have the ligand that stick to these receptors. They get into the endothelium. They cross through the cell without tearing open the blood-brain barrier, and they end up in the brain. So this is not theory. We published this in Nature a few months ago, and this is what you see.

If you look at the brain on the left, and actually this is taken from the same brain, just the one on the left did not have ultrasound, but had intravenous administration of exosomes. You see a few white dots there. We know that no more than 5% of the exosomes given intravenously get into the brain. They can go anywhere, not just to the target you're interested in.

Look at the brain tissue on the right. This is exposed to ultrasound. What you see is a starry sky of white dots. Those are all exosomes that have been facilitated in their delivery because of focused ultrasound to the target zone. This is very specific and very efficient. At least 50% of the payload given intravenously ends up in the target zone. Not in the liver, not in the kidney, not in the spleen, not in the lungs or wherever else.

and also in the part of the brain that we're interested in. So, what have we done in humans? Well now, this is an old slide, but we've treated over 100 individuals with this technology. And I should always be very careful about presenting this data to an audience. So the FDA requires that in the United States this is only done in the context of a clinical trial. So, we've done this without any side effects in humans.

We've looked at several different situations where brain optimization was required. So we looked at individuals that wanted to reset the biological clock. Of those individuals where they were asked to rate how significant their change was, their improvement was, 94%. Targeting other structures like the hippocampus in Alzheimer's disease, 52% for a single treatment.

Reset mood targeting, and we've published this material as well in Brain Stimulation, 64% recovery. And these were patients that had failed ECT, failed multiple drugs, weren't getting out of bed, were suicidal. 64% got better. Remission. Then modifying Parkinson's was a 73%. So what does this do for an individual when you reset a clock in humans? And I've done it myself. So I'm 75 years old.

And if you look at me from performance measures, methylation clocks, telomere shortening, et cetera, I'm like a 50-year-old. Lowered stress, you could scream in my face, I'd be just fine. Improved recovery after exercise, improved deep sleep. I only had 15 minutes of deep sleep that I was tracking before treatment, after treatment, over an hour. And you need deep sleep to clear out those toxins that accumulate during the previous day.

more energy less body aches and pains my skin hair this is real hair and improved drives which brings up a couple of the side effects i think these are kind of good side effects that should be anticipated well first of all here's an individual i don't know if he's in the audience right now but here's an individual who was getting weak sarcopenia in his 60s after getting treatment

When he went to Hawaii, he started climbing trees barehanded, and this is a picture of him doing that. Now, I'm saying this is a side effect. I'm not sure it did enough for this individual's frontal lobes because he made a bad choice. He climbed up a very high tree with a weak bow, fell off as the bow broke, cracked seven ribs, and then had to recover from that. So here's another complication. This is my wife.

She's in her mid-60s. This is after treatment. But I'm saying there's a complication here because when I got treated and my drives were improved and my hair grew in and my skin looked better and I looked younger and I had more energy, she had to have it too. Now, in a public audience, I can't show you the baseline photographs because she would kill me. Now, this happens to be me. So before one of these treatments that I had, which I do once a year,

Just fortuitously, I herniated a disc. And you can see that here in the MRI scan. So there is an edematous disc, there's a fracture of the end plate, and a little bit of an annular tear. I couldn't get out of bed. I had severe muscle spasms, severe pain. Don't tell me a joke, because it would hurt to laugh. It went away within less than a week of getting this treatment. And why is that?

It's because the two main inflammatory systems in the body are controlled by the hypothalamus. So as you know, the adrenal cortical system, that's a big deal. And the other part is the vagal anti-inflammatory network is controlled by the hypothalamus. So both of those were reset. My pain went away immediately. Didn't have any surgery. I was thinking of getting an epidural. I was thinking of getting steroids. Didn't do it. I'm fine. So what does the future hold? We're going to have improved targeting

in the brain with imaging. Our advanced imaging, you show us from Dayan, that's some of the material that I worked on with Dayan. We're able to look at things in ways, and I'll show you a little bit more about how this looks.

We have improved stimulation with advanced generation ultrasound. So I'm showing you results from first generation. We're now on to third generation. I'm going to be the first one in the world to receive this this coming week. We have the ability to give more energy. We're able to take care of the aberrations of the skull. We're able to generate different energy patterns based on skull thickness. And we can actually visualize the ultrasound wave and how it intersects with our targeting zone with a great deal of accuracy.

And plus, this is really cool. Right now we're just giving exosomes with whatever cargo is in them, but we're gonna have designer cargo eventually. We're already designing experiments, so look at this. So how about giving some genetic code encased in an exosome and deliverable with ultrasound as an example? It needs to be sent to the next slide. It's not changing. There you go, thank you. So this is an example of what I was talking about

So the hypothalamus has multiple nuclei. With advanced ultrasound and increased precision, increased focal points, we can pick out very small areas of interest and target them for delivery.

So the hypothalamus, if you wanted to treat obesity, if you wanted to treat sexual drive, if you wanted to treat a sleep-wake cycle disturbance, we can go after those nuclei in a more precise way. So that's what the future is going to bring. Think of the following. The nucleus raphe that produces serotonin in your brainstem, we can reach that with ultrasound. How about giving genetic code that turns on the serotonin production in someone with depression?

so they get the serotonin that they may need to improve their mood. And then if we have too much, we can use a controller gene to turn it off at our will. Do we need to take a drug that has all these side effects? We can just reprogram the cells involved to produce something different. So last thing I want to talk about, we're running out of time, is something that I find to be interesting, disturbing, and so far an area of interest

and worry. We know that during your lifespan different parts of the brain develop. They appear to be controlled by remnants of old viruses called transposons. I don't know if you know this, but only 1% of your genome actually codes for your proteins. The other 99% does something else. The majority of that something else are remnants of viruses that are incorporated into our genome.

They help turn on some of the development of the brain. And it's very interesting that when they turn on, they do it in a way which is very interesting and will be further discussed by the next speaker, Dr. G.M. Papa. So normally your genetic code is coiled away tightly in dense chromatin. And it's only when it's unraveled, so here's the dense chromatin, when it's unraveled, then the genes are exposed

they're de-repressed and they're able to produce proteins. At the same time, these transposons are de-repressed and they become available for whatever environmental stimulus, including inflammation, that triggers them to produce problems. So why does autism occur around the time of speech acquisition and socialization, early mother-child attachment?

Why does depression initially occur when socialization parts of the brain are being developed in the teenage years?

Why does schizophrenia occur in the 20s when the frontal lobe is being developed with these transposons triggering them? So line one transposons appear to be responsible for producing the development of our frontal lobe that makes us the humans that we are, but also exposes the genetic code to various kinds of toxic elements that can produce something like schizophrenia. But let me get back to aging and then we'll be done.

So Alzheimer's disease, Parkinson's disease, ALS, all these degenerative conditions that are age-related, they come on in old people generally. It appears more and more that these transposons are playing a causative role in these conditions. So there is some genetic code that's typically wound up tightly that cannot be exposed to environmental insults that is now exposed. But what is that gene?

So is there a Grim Reaper transposon? Let's call it the death gene. So as I said in the very beginning, death is good for the species. So aging is good for the species because at times of stress, you want to kill off the frailty people, but not the ones that are of child-rearing age because that's what sustains the species.

So nobody has really thought about this, but it occurred to me that all these aging-related diseases appear to be related to these transposons. So something's unraveling, but what is that something? So the future is improved targeting in the brain with imaging, improved stimulation with advanced generation ultrasound, and designer payloads for exosomes. In summary, a central clock in the hypothalamus controls aging.

Restoring function with young exosomes appears to forestall the aging process. This is a matter of further discovery and study. Animal experiments demonstrate that low-intensity ultrasound may be used to facilitate delivery of exosomes to the brain and reprogram the central clock potentially. And the human trials appear promising. So I will leave you with this idea that aging is not a requirement. It's an option.

So let's all work together to make this a reality. And that's all I want to say. Thank you. If you are enjoying this program, please hit that subscribe button or even better, leave a review. Your support makes it possible for us to create the quality programming that we're continually striving for. Can I start? It's already recording. Oh, sorry.

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