[00:00:00] Hey, hey, welcome back to another episode of superhuman radio. One of my favorite topics today and has been for the past 13 years is anti-aging but you know when you talk about anti-aging to mainstream people. They immediately think of some sort of face cream that makes you look younger when we talk about anti-aging we're talking about mitigating or slowing age-related diseases living longer greater Vitality greater Health span.

Lifespan is not enough if you spend the last 30 years of your life in a wheelchair at a facility facing the wall, that's not that's not any kind of longevity. We want we want to be fully engaged in life as we age. And while it looks like through Evolution, we did a better job assuming that we didn't get [00:01:00] an infection or impaled by a farm implement at staying rather robust as we age diseases of my journey and the sick aging phenotype is very familiar discussion on this show.

And in a moment, we're going to be talking with dr. Paul Robbins about some breakthroughs that show that maybe it's possible to actually reverse aging we've talked a lot about aging better and there's lots of things that are Punic approaches diet intermittent fasting lots of good stuff out there that shows us how we may be able to age better.

But what about actually reversing some of the broken stuff? We're going to be talking about that in just a minute. Of course. I have to thank our title sponsor All American pharmaceutical and EFX sports right now. You get six of their top selling products absolutely free by going to superhuman radio dotnet and clicking one of the EFX Sports banner ads putting in your name and [00:02:00] address in there and five dollars and change for shipping and you will get six of their top-selling products absolutely free because

Dr. Jeff Golini believes that no one should buy anything until they've tried it. He puts his money where his mouth is. Welcome to the show. Dr. Robbins. How are you? Just fine Carl. Thank you for having me. No, it's very exciting to have you this is one of my favorite topics because people think that I talk about anti-aging for selfish reasons and and they are selfish, but it's not about looking younger.

It's not about buying a Corvette and chasing young girls. It's about staving off age-related disease. Isn't that really the core of the important research that? That's correct. I just point out the week view it not necessarily anti-aging but we're just trying to extend health span. I think trying to reverse aging is going to be more difficult than slowing aging.

So as you [00:03:00] just said is trying to stay healthier for longer stay of the wheelchair stay out of the nursing home sale the emergency room. So that's what we're trying to do and whether we live longer while doing that if extend health span, that's also good. But the goal is to make us age in the healthier way and you know, I'm glad you pointed that out because I.

I did something about seven or eight years ago. I stood outside of a Kroger's grocery store and I polled people and I asked them. Do you believe that you will get a disease in your lifetime and the great majority of them said yes, so it's almost become the norm to expect disease as opposed to expect health.

That's absolutely true. But obviously we all die from something and so the key here is to just delay the onset of the inevitable age-related diseases. We are going to get and then have [00:04:00] that period of morbidity where we're starting to develop one or more of these age-related diseases to compress that so we're getting healthier for longer and sick for a shorter period of time at least that's the concept that we're trying to do in our approach and the Aging field.

So real kind of a Reader's Digest version of the various theories that have been promoted over the past hundred years or so that have tried to answer why we age in the first place. If you can kind of just give us like the synopsis to where we were what we looked at what we figured out is it and now where we are today?

Right, that's a great question. And so obviously aging is much more complicated than anyone disease or any type of cancer for example, but with the field currently is that there are now considered to be seven or eight pillars of aging and these are factors [00:05:00] that contribute the driving aging and these include metabolism the ability to adapt the stress just damage to your cells in your body chronic inflammation loss of endogenous.

I'm cell function and then one that we have become very fascinated with more recently cellular senescence, which is a process where cells if they acquired damage stop growing and then they start sending out danger signals that tell them you system to get rid of them because they're damaged and those emergency signals.

They send out to the immune system are inflammatory factors and actually will stimulate a low level of inflammation and damage the tissues and. A lot of evidence now, but these damaged cells these cellular senescence cells contribute to driving the aging process, but all of these different pillars contribute and they're all length.

So stem cells are adult stem cells are involved in repairing damaged tissue. They actually become senescent with age and so they become dysfunctional and these [00:06:00] bad factors. This Nestle's release into the bloodstream affect metabolism. And other components of Aging so they're all Linked In. So if you improve one of them, you probably wouldn't prove the other pillars of Aging.

Okay, my first ever interview about cellular senescence happened in around 2007 and it was a study and I looked for it today, but I couldn't find that I've gone and I've changed computers so many times over the years, but the study propose. Or promoted the notion that cellular senescence was triggered by glucose.

Did you do you remember any of that sort of stuff? I mean because dietary, diet has an effect on this as you mentioned a moment ago, but I high-fat seems to do it as well. Is there an intersect between glucose signaling and high fat diets that seemed to Herald cellular senescence or is it just the fact of the raw throughput of all of these calories [00:07:00] to us kind of like if you burn 10,000 gallons of gas your engine is going to be worn out after.

Well, they've shown that that animals the mice or other model systems on high fat diet develop more senescence particularly in fat tissue and this contributes the driving some of the conditions that animals that eat poor nutrition develop. And so if you actually get rid of these damaged cells it's necessary.

It actually improves metabolism reduces inflammation and extends health span. So yes, I think that paper remember is one of the first ones are really starting to link some of these metabolic phenotypes with age to Cellular senescence. And then and then people like, oh he was on my show the guy from England.

It'll come to me Aubrey de grey. He was a big proponent of the mitochondria. Theory of Aging that the more your mitochondria works the more reactive oxygen species and oxidative stress [00:08:00] it puts on the body you age faster have we dispelled that or is that still kind of. We actually just had the manuscript published last year at that strongly supports that model.

But again, everything is linked. So if your mitochondria become dysfunctional they start to make reactive oxygen that then can cause damage to your DNA that then stimulates Pathways that lead to Cellular senescence the mitochondrial dysfunction. Oxidative stress they all lead to increase in the senescence L burden of the body.

So if you use antioxidants that we do sailor senescence things that improve mitochondrial Health also reduce senescence. So again, they're all linked and so we had been became interest Insider senescence because we thought that maybe a better Target than some of the other pillars are Pathways that were discussing that we can maybe developed approaches to.

Target them with drugs well, and your approach actually makes sense from a therapeutic standpoint and that's [00:09:00] what because regardless of where we are getting cellular senescence from you have targeted the actual senescent cell and saying look we're not going to split hairs about why this happens, but we do know that if we can either remove them.

Or reverse them, the downstream effect is a very positive one. So let's let everybody else postulate and fight why it happens. We're just going to focus on the cell itself and say look now, there's some research out there that I've seen and I think your person in the media Department sent along to me as well that shows that when they transplanted a senescent cells into rodents the rodents really started to age and show.

The the signs of aging is that correct? You have been so there was actually really two sets are three sets of experiments that changed the view of the role of senescence cells and aging and the first was [00:10:00] actually making transgenic mice so that you could using the genetic trick eliminate senescent cells as they accumulate with aging and if you did that my stage in the healthier manner, so it shows you got rid of the cells that in approved the health span and then some.

This is the lifespan. The second was developing drugs that actually would do the same thing as a genetic tricks. So using drugs that we've identified that will actually kill these damaged senescent cells. And then the third is what you just referred to was if you inject senescent cells that you generate in the laboratory into a mouse or a rat this will drive frail to yield right metabolic disease.

It will drive signs of accelerated aging. So this shows that. You've damaged cells really are driving force for aging not just the consequence but they actually drive the aging process. But have we seen the reverse have you taken age [00:11:00] rodents and either put non senescent cells in them Ryan do those do those then proliferate and kind of level the playing field inside the.

I think you would say that we've actually reverse aging there's always a difficult thing. I think we've shown is that it slows the rate of Aging you might see Improvement in certain tissues and I think the reason why is there has been several published reports and we have data that very similar that if you eliminate senescent cells are produced us nests and sell burden.

It improves the endogenous stem cell function. So one of the reasons why stem cells become dysfunctional with ages because either they become senescent some of them or senescent cells near the stem cells releasing these bad factors lead to Stem Cell dysfunction. So if you improve endogenous stem cell function, then they can repair damaged tissues more effectively.

And so there may be certain. Age-related conditions that are [00:12:00] improved not just slowed but improved by eliminating senescent cells. I'm not a scientist but I whenever I think about this and I think about it often because I am 60 years old now and I do want to live a long time and I want to be healthy for that period of time and I know I'm going to die, but when we look at some of the function hyperfunction malfunction approaches to.

Aging to try to explain aging it almost seems like in order for us to really reverse aging we have to do two things that a diametrically opposed to each other the first that you've described so eloquently, but the other one would be to kind of turn on neonatal genes that are responsible for the exact opposite.

Of what we're striving for on one side of the table to get them to actually open up the blueprints and go. Oh, here's how we rebuild that is that [00:13:00] is that is there a yin and yang here? Ultimately someday, you know years ahead of us. Yeah, well, I think we have a long way to go. I guess the best example of what you're talking about is there's technology been developed that you can take any cell in the body and reverted to a stem cell or type of cell that sends be similar to a stem cell and you can do that with just activating three or four genes in the cell.

One day I'll revert it from a differentiated cell like a skin cell into a stem cell and to a genetic trick. They showed if you partially reprogram cells in an older Mouse to be more like stem cells that it actually kind of reset the Aging clock. Now this approach the mice is not something is going to be applied to humans, but it does show if you can reset the clock and turn on younger [00:14:00] genes that it can have a benefit.

The problem is always that there could be an adverse effects right in addition to making this little bit younger section increases the risk of cancer. So these are things we have to look at very carefully and what we're doing now in animal models is not ready for prime time and people but having said that the approach that.

Number of people are taking including my life. Instead of trying to reprogram or make the stem cells in the mouse or human more effective. We actually are taking young stem cells and introducing them either with or without drugs that can kill these senescence cells. And that to seems to have a dramatic effect on slowing aging potential even reversing certain aspects of Aging.

So I think it's going to be a cocktail of approaches that will be needed going forward but there's really no one approach that's going to change everything but [00:15:00] it's going to be a cocktail that many different types of drugs that Target all these different pillars of Aging take can you before we go into our first commercial break?

Can you touch on I did my first show on? Blood from young to old. It's actually three years ago the first time talk about and whether or not this Nosferatu had the right idea approach actually is Meaningful in the research or is it just two Macabre most clinicians like we're just not going to go there.

Well, and there actually are clinical trials currently ongoing and their companies that are selling young plasma if you want to purchase it, but that the date is fairly remarkable. What it shows is that there's something in young serum there factors which are still poorly Define that can slow Aging in an older animal and if you take the same plasma from the older animal and put through younger animal there factors [00:16:00] that stimulate aging.

So what you have is you have this balance of good factors in the young serum bad factors in the old that modulate aging and so the billion-dollar question is going to be what are these factors is find out a single factor is got to be multiple factors that either drive or slow aging and so their clinical trials have started at Stanford Tony whites Cory who's been a leader in this field for a while Tom Brando.

They are treating at least. Stage Alzheimer's patients with young plasma because they've shown in Mouse models this improves cognition in older animals. So they have started these trials the FDA has no issues with them because people do blood transfusions all the time. So it's it's not regulated because it's a standard procedure.

So they're using plasma much Lucky from Stanford medical students or our young individuals over 18. See if they can slow the progression of Alzheimer's disease [00:17:00] and the data from The Phase 1 trial. It's been someone's been reported. I think there's some things look promising some things they have to look at in more detail.

But this approach is getting a lot of publicity clearly young plasmas not going to approach to treat millions of people to keep them healthier for longer, but the important point is going to be to identify what these factors are and that's where everybody's putting a lot of focus both companies.

Academia because that would make a huge difference to human aging if we could identify what these factors are. I want to take our first commercial break when we come back before we delve Deep dive directly into your research. I want to I want to introduce the role of the immune system because I keep whenever I hear these kinds of stories, like for instance, I several years ago.

I did an interview where they showed that old and [00:18:00] young rodents. They received an injury to a muscle the young rodents naturally healed quickly the old rodents didn't but then they gave some other old rodents oxytocin and they age just like young rodents and then I did a show shortly thereafter that showed that oxytocin increases a microbe in the gut called el rotary which is associated with better Aging in rodents.

And in and they think in humans and I started to understand that there's this kind of symbiotic relationship between the outside and the inside of our gut and the hormones and different things in our blood may play a role in the proliferation and protection of certain things in our gut and that they will talk about the immune system.

Whenever we talk about the gonna have to remind everybody. Hey when you're talking about the immune system will talk about the gut. I want to just. Have your opinion on that discussion and then we'll [00:19:00] dial delve into your research directly. Okay, sounds great girl. Okay so very much sit tight. We'll be right back with more superhuman radio.

Welcome back we're talking with dr. Paul Robbins from University of Minnesota about some emerging research on. Well, improving Health span by focusing on what happens as we age. So going into the break I did this whole connect-the-dots thing that happened for me over the past several years where I started to look at the immune system either as a willing participant or possibly the beginning of many of the changes that occur in aging especially when I started to see research coming out that showed.

Hormone levels affected certain gut microbes that are affiliated with immune function and an aging, / you know kind of Aging better. What's going on with all that is it where's the cart? Where's the horse in that relationship? Well, I think there's still a lot of questions to [00:20:00] be asked about the role of the microbiome which plays a very important role but we're not quite sure exactly how that regulates aging but I think the role the immune system in driving aging systemic aging and including leading to an increase in susceptibility to infection and cancer the immune system aging probably plays a larger role at aging than we've appreciated we and others have now shown.

Because if you take aged immune cells are age the immune system specifically, it seems a lead to systemic aging and in the reason why we think this is true is that immune cells become senescent as you get older and so your T cells and B cells and other immune cells become senescent release these bad factors and because they're circulating throughout the body.

They go everywhere and can release these bad factors. And so they contribute dramatically. To the aging process and then the flip side is that if for young [00:21:00] and we acquire these damaged cells, it's our immune system to clears them because that's what this whole process of senescence has evolved for is to get rid of damaged cells and then your immune system comes in and clears them.

But as we get older and our immune system starts to fail, it doesn't clear the cell. As well, so we have to kind of a two-edged sword. They're not clear as quickly in the D cells also drives senescence. So we think the immune system is going to be a very important Target for drug development and many of the same approaches being developed to stimulate the immune system to fight cancer can also be done to try to eliminate these senescent cells and improve immune function and I want to go on the record.

I've said this before I'm starting to realize. That the majority of diseases of modernity are in some way shape or form associated with [00:22:00] the immune system more every day. We have new connections between the development of Parkinson's disease and autoimmunity now glaucoma has been attributed to autoimmunity.

You know, I know heart disease is the number one killer. In America today, but I am not convinced that heart disease doesn't occur also from some form of autoimmunity. And when we really look at it 76% of Americans claim to have gut issues the rate of distended stomach SIBO is now being taken seriously by a Anthem and other big insurance companies because they realized that if they leave it and ignore it these people tend to get sicker faster.

We you know, I keep coming back to I think I keep thinking myself my God, you know the term hypochondriac was coined by Hippocrates and it Loosely means below the rib cage. These people had symptoms that couldn't be explained and pinpointed but they just kind of felt it and [00:23:00] hypocrisy said this is it's happening in the gut and that's what that's what.

That term means hypochondriac and I'm starting to come to the realization that we if we can fix the immune system and the gut we may be able to eradicate a lot of these diseases now, that's my own little statement. I have no medical degree and nothing anybody can you know license medical licensure board can take away from me, but that's what I believe talk about.

Now. Let's talk about your study specifically talk about the design of your. All right. So what we did in this is started in collaboration with the Mayo Clinic, I would Jim Kirkland who's a leader in the Aging field and also leader and cellular senescence and understand its role in driving aging but we set out to see if we could identify drugs in particular FDA-approved drugs that could be repurposed to actually kill these damage senescent cells.

And [00:24:00] so we develop approaches the be able to screen drugs and the laboratory for those which might preferentially kill these damaged senescent cells and not a normal healthy cell and what was interesting and during the course of these experiments. We started to realize that these damage senescent cells are very similar to tumor cells.

Because they've acquired damage and in theory, they should be dying because they're so damage, but they don't and it's because like tumor cells they upregulated or have higher levels of things that prevent them from dying and so drugs have been used in the clinic to kill tumor cells up here at least some of them appear to be very effective at killing these damage senescent cells.

And which makes sense because what cellular senescence is supposed to be doing it was actually developed through Evolution to prevent cancer. So if you have a mutation in the cell that stimulated that cell to [00:25:00] start growing. In an uncontrolled way this pathway the stimulate a senescence phenotype is stimulated to stop tumor growth.

And then the release these emergency signals to tell the immune system to clear it. So that's how we would get rid of precancerous cells. And so the senescent process is actually probably there to reduce the risk of cancer. And so drugs that killed these pre senescence are I should say precancerous cells those drugs also appear to kill senescent cells.

So the first thing that we showed was is that the drug called the satin Deb that's used for many different types of cancers been the particular certain types of lymphomas. That this drug in combination with another compound with kill these damaged senescent cells just like a tumor cell and if you treated mice with these even mice that were already two years of age which would be roughly our age car all around 60.

If you start [00:26:00] a treatment that age intermittently to clear these damaged cells the mice were now healthier and they live longer. And they had fewer senescent cells. So this is very exciting. But it turns out that this combination drugs is probably not the only combinational kill senescent cells and so other clinical use anti-cancer drugs that are supposed to kill tumor cells specifically also people to kill at least certain types of senescent cells.

And so the first clinical trial I should say clinical trials for these. Have started not for aging per se but the look at age-related diseases where we know senescence plays a key role in driving the pathology associated with disease such as pulmonary fibrosis chronic kidney disease, even osteoarthritis are all conditions that are now being treated with these are at least in Phase One or Phase 2 treated with drugs is the kill the senescent cells to see if we can reduce disease pathology.

So does this [00:27:00] do this selectively? Hit these cells and leave healthy cells alone or is just the relative Fallout to a healthy robust cell just isn't that bad? They probably have effects on the healthy cell but the Fallout isn't as bad because they don't have all these damaged Pathways activated and then these Pathways to prevent that cell from dying because of these damaged Pathways and be inactivated and the beauty of it.

I mean the beauty of using these drugs that kill senescent cells is they don't have to be given Chronicle. So for cancer rifle take the satin to have chronically for a long period of time because one tumor cell can start pull if writing again, but what we're trying to do is just reduce the senescence L burden and it probably takes weeks if not months for the senescent cells that come back.

So the theory is as you would give these treatments once a month, maybe [00:28:00] the once every six months and that we reduce the senescence burden without. I've been in the long-term toxic effects on the normal cells what more least please that's the concept that we're trying to take forward into the clinic and that makes perfect sense that really does but okay talk about the role.

Of course certain as part of this is cocktail because quercetin while it people think it's a really good antioxidant the two interesting things about courses in that I learned many years ago, is that they seem to. Search ruins to a small degree but more importantly it seems to reduce igf-1 conversion from growth hormone does.

Yes, of course that does a lot of different things and so the problem with using that that you don't know what the specific Target is. We chose it because it was shown one of his activities when it was many activities was targeting a specific component. [00:29:00] That Pier to be upregulated in the senescent cells just like tumor cells and we've shown that you can bind corset and with the satin if that that combination was seem to be more effective at causing deaf and only certain types of senescent cells and appears in mice at least that this combination is more effective at clearing senescent cells.

Why or how quercetin doing? This is still not quite clear because it has so many different targets but having said that we've now shown that other related compounds not quercetin but ones are very similar probably work even better and then we can do Medicinal Chemistry and make him even better than that.

So we think the quercetin although good can be improved upon tremendously and we think the  is just one of the many anti-cancer. Which also will be able to lead to death of the senescent cells release of certain types? And I should point out [00:30:00] I'm talking about senescence and it's there's probably different types of senescence and probably different tissues have different types of senescent cells.

So it's not like it's just one type of cell there's probably a variety of types of senescence and that's what the field is now looking into more detail is really what are the key types of senescent cells that drive aging. Where are they? What tissues such as the immune? And then can we identify drugs that Target this specific subset that seems to be important that's reversing aging.

So you said there are other agents besides quercetin. I got a Brooklyn accent. I'm stuck with it. But anyway, how about how about the gingerols found in ginger. There are several good studies on cancer and its effect. Gingerols, especially the six and the eight forms.

It shows that it reestablishes the apoptotic landscape and cancer cells [00:31:00] just die on their own and it also is inhibitory to cyclooxygenase. Oh, it has an effect on inflammation. It would that be also a good choice with the . It's something that just you describe that it could work.

I'm not aware of anybody. We've not looked at it. I'm not aware of anybody else who's looked in the combination, but the rationale for it makes perfect sense. And so what we're doing is we're trying to do. Kind of rational design rational thought Ford for identifying compounds which might work synergistically with either descent and every course that and or we just we have published the things targeting the heat shock protein or a chaperone protein that helps proteins fold hsp90.

If you block its activity that leads the prefer preferential death of senescence cells. And then also there are a number of anti-cancer drugs that. Get what's known as the bcl-2 family proteins and these are [00:32:00] proteins which are known to prevent cells from dying and they're very Express much higher levels in tumor cells and that class of drugs has been shown to be very effective in a sexy that class of drugs that Target bcl-2 that's in the clinic for osteoarthritis.

Yeah, because we now we now know osteoarthritis who also has its Beginnings in autoimmunity now at the it was always thought that just rheumatoid arthritis and things like psoriatic arthritis. Well were autoimmune disorders, but now we realize that relatively lean people whose joints don't experience a lot of accountable loading have inflammation that destroys chondrocytes and they've even attributed that a saying hey, you know that that osteoarthritis actually found it Finds Its Beginnings in in autoimmunity.

Is that right? Well, I there are a number of reports is say that there's an all the immune component to osteoarthritis like rheumatoid arthritis, but the data that's coming out in regard to senescence [00:33:00] in osteoarthritis is that if you look in the cartilage of individuals with osteoarthritis through a large percent of those cells which are senescent and if you clear those senescent cells again using one of these drugs.

The son Luke drugs. I've been discussing that improves pathology at least in animal models of osteoarthritis. And so one of the problems of senescent cells is they release an inflammatory cytokine called il-1 and I'll one is probably a key driver of cartilage destruction. The number of drug companies who are trying to develop things that Target il-1 because it is what leads to degradation of cartilage and senescent cells which appears.

Chondrocytes can become senescent which may be because of the weight just mechanical stress may be a variety of factors that those senescent cells of the rise because of the stress release aisle one that leads to cartilage destruction. Interesting. I want to take on next commercial break and when we [00:34:00] come back, I want to come back around and talk about the immune system and some of the research that's being done on the anti-rejection drug that's given to people who have had organ transplants.

But obviously they take a chronically ongoing for the rest of their lives, but then seems to be some benefits from intimate and exposure to rapamycin. And I'd like you to talk about that in our next discussion. Okay, sounds great. I stay tuned. We'll be right back with more superhuman radio

many of you know that my approach to science change in 2014. When I had dr. Daniel Lieberman on the show and we talked about his amazing book The Story of the human body every scientist every lay person. Every person should read it to understand the. Of humans throughout Evolution and why we have the things we have that our gifts and why modernity seems to challenge them.

If you haven't had a chance [00:35:00] to read the book and every time I talk about it you go, you know, I got to get that book. I got to read it. I have an opportunity for you to literally absorb all of the Salient information in that book in 15 minutes. You've heard me talk about. An interesting new app that I discovered recently and I've talked about it because I keep telling people you've got to get on the program.

It's called http://blinkist.com/superhuman and they reduce entire books to a 15-minute audio of blinks and they break everything into segments and they give you all of the important takeaway information from a book in 15 minutes on your commute,. your drive, your on the treadmill doing your cardio. You can absorb all the information and they have over 2,500 non-fiction books to choose from and guess what one of them is it's The Story of the Human Body.

If you go to http://blinkist.com/superhuman  [00:36:00], you'll get a 7-Day free trial and I'm telling you your brain will thank you, so don't put it off another minute. Check it out. We're talking today about wonderful anti-aging approaches. So what do you think? What do you think about the this this?

Merging information about anti-rejection drugs that seem to just shut the immune system off for one day every two weeks and promised to help us eradicate some of the diseases of my of age. Is it so the compound you're talking about? The drug is called rapamycin, which has been used to suppress the immune system and Transplant individuals transplant recipients.

But the dose they use of the rapamycin is much higher than what has been shown to extend lifespan at least in lower. Vertebrate systems so it's been shown in Mouse models that if you put them on rapamycin starting either early in life or even now older and life that it will lead [00:37:00] to a life extension and healthier life span in both male and female mice which is important because many drugs which have been shown to have effects at least in mice effect either males or females but not necessarily both which is an interesting observation.

The rapamycin has been shown to affect both and so it's now being tested more in the laboratory. But also in the clinic giving it either intermittently or for short term period to see if he can improve the certain conditions and I think the best example was published last year from Novartis where they tried to determine if treating.

The elderly with rapamycin for a short period of time with improved immune function not suppress it. But improve it leading to a better response to the flu vaccine. So they put people in their eighties on rapamycin for a period of time took them off gave him the flu vaccine and showed they had a [00:38:00] much better immune response to the vaccine and age-matched controls that were not given rapamycin.

So this is very exciting. And so they're now trying to figure out exactly how big is it? How long when the start to see if you can ameliorate other age-related conditions in humans and another exciting observation that was made or I shouldn't say observation but clinical study it started University of Washington where they are now treating.

Dogs with rapamycin to see if it looks 10 the lifespan or house band of canines in the rationale is unlike laboratory animals that aren't in the same environment as humans dogs, share a house share many of the same environmental cues as humans. And so the question is if you put them on drugs like rapamycin will they see an improvement that could be similar to what their owners would see if they were taking?

So they're now doing a rapamycin trial to see [00:39:00] if it improves Health span the lifespan in in pets and dogs, which is a very interesting approach and I think the initial data is looking very promising. Okay. So let's talk about the immune system for a second. You corrected me when I said it suppresses the immune system.

No, I that's true at high doses. It's that's the reason that's given to the transplant recipients is right presses the tmb cell responses. So that is. True, but in this in this approach, isn't it still suppressing the th2 immune system the learned the acquired immune system because isn't the whole problem with flu vaccines and a lot of the other things that they stimulate antigens, but the one portion of the immune system really doesn't get activated.

So it's not truly embedded in the immune response and when we look at. Some of the things that we're seeing today with immune systems going awry where they're [00:40:00] attacking thyroid tissue or chondrocytes and stuff like that. Isn't this just a you know in laypeople terms. I mean, I'm just an average guy just an imbalance in the in eight verses the Learned immune system and rapamycin seems to kind of go.

Hey everybody. Let's get along. Let's just calm down for a. Well, so the enzyme at Targets which is the it's actually was named the mammalian Target of rapamycin because that's how was identified as the target for this this drug regulates. A number of Sailor process these it regulates the cells response to amino acids the nutrients to a variety of environmental cues that stimulate a cell to grow or to stop growing.

And so if you use this drug, it doesn't variety of things and it depends also on the dose and how frequently you give it. So it does kind of reset the immune system, but it also improves. The Aging immune system [00:41:00] because it's been shown that actually reduces. Things that go wrong in senescent cells.

So if you treat a senescence seller rapamycin many of the things that the senescence cell does goes away. It doesn't release these inflammatory factors. It doesn't release these emergency signals. So it actually has been shown to suppress senescence. It doesn't kill the cell but actually suppresses these cues.

So one hypothesis is that what rapamycin is doing is that it's reducing senescence in the immune system, but also in other tissues. So that's one potential mechanism. There's probably about five others 10 others. So it's very complicated process, but it depends on the dose. How often you give it what age you give it and so there it's very exciting their trials now ongoing for Parkinson's for Alzheimer's because there's been very good preclinical data using rapamycin and that setting and then rapamycin has a few side effects.

So a number of companies are planned effort [00:42:00] in developing what it called Rapa logs, right? Sir, similar compounds that may not have the side effects. So rapamycin has been shown if given that high dose to cause testicular atrophy, which is not something that aging males with want to have right now.

They're trying to see if they can find things which are little bit safer. It's also been them rapamycin has adverse effects on beta cells so it can affect your metabolism. And so they're trying to find these beta cells in your eyelids that release insulin and so they're trying to find versions that maybe don't have this adverse effect on beta cells.

So in some of these new rapper logs are now in the clinic for number of different conditions including cancer. Well, okay. So those of us who are Avid weightlifters, which this oil is made of we know the importance of MTOR one and mtar-21 c and so on right now because this [00:43:00] is a stimulates protein synthetic response.

It's acted upon not only by. Muscular loading but also nutrient amino acids like leucine. So when we talk about MTOR in the context of cellular senescence, does that mean that those of us who tend to work hard to maintain the amount of lean body mass? We have as we age or doing ourselves a distrust and adjust.

It's a great question. I would say not I was saying that you know and toward doesn't very good things. It does some things that if it's too elevated may not be good. So there's no evidence that exercise is bad for you in any way. In fact all health studies show that exercise including weight lifting again, maybe not to the extreme but within reason.

It's very beneficial reduces senescence extends house band and improves memory improves cognitive function that does a variety of things so muscle mass is extremely important. So it's just MTOR [00:44:00] regulates more than just protein synthesis and cell size. It regulates a variety of other things in response to signals.

And so I guess one example would be is that. One thing that's known to lead to extension of lifespan the least in in mice and other model systems, its caloric restriction, right and that's partially thought to be due to limiting specific amino acid uptakes which regulates. Presumably on tour so cork restriction may be eliminating the certain amino acids from your diet.

They all seem to have effect on them tour activity. And so that's probably at least one of the mechanisms through which clerk was friction has had this benefit the problem of clerk restriction that's not all species respond in a positive way to it. So if you take out 20 different Mouse strains, A few of them will respond well to clerk restriction that live longer.

Some of them will actually live shorter. So that's the [00:45:00] problem with the field is trying to figure out who's going to respond well to a certain drug or a certain nutrient intake or are reducing caloric intake because even then animals such as the mouse or rat. There's huge differences between strains and which makes us all very complicated right and humans too.

Okay. So one of the things that has come about in the past five years now and started but back in adopters to Phillips is lab up at McMasters is that perhaps caloric restriction isn't as necessary. If we I hate the term intermittent fasting. I I like to say a more ancestral feeding. Pattern you know before we had refrigerators in cupboards and maybe even before we had modern agriculture going back past forty thousand years.

We ate probably not first thing in the morning we have we usually had to go out and find food and even dr. Milind Watve’s book of doves diplomats and diabetes [00:46:00] seems to illustrate this this in today's dialogue piece. So we are learning now that you can actually buy timing, you know having a smaller feeding window a larger fasting window.

You can actually stimulate a lot of the same. Metabolic mechanisms that we see in caloric restriction, but without actually starving yourself and we also learned two years ago. I did a show that showed that the role of Basil or tapa G plays an amazing part in protein synthesis that in fact stimulating autophagy.

Which generally only occurs when you're not eating actually promotes muscle growth to a greater degree. When you give an iso-caloric diet to two groups of trainees that are working out and one group is breaking their meals up into more frequent meeting eat and the other group is just eating three times a day those periods of otology actually helps stimulate.

Protein said that it said that a response by cleaning up [00:47:00] the waste products from the workout. So it's starting to play out. Now that you know what maybe we don't have to starve ourselves. We just don't have to eat so frequently and the other interesting thing about fasting is it also seems to have a direct effect on kind of quieting the immune.

Absolutely true and like so what's interesting when you when you talk to scientists in the Aging field about what regiments they follow. What did they eat L often lead you realize that there's nobody believes in only one approach. I know scientists that are really limiting calories are the ones who only eat for five-hour window during the day they say I don't care what I eat as long as like either only in the five-hour window.

And so you get this whole Spectrum some people taking Resveratrol some people taking that and they D precursor some people now trying to take a drug that they think [00:48:00] acts as a send a living to kill the senescent cells. So it's really interesting about what the different approaches the scientists who study this are taking and you realize there's no consensus but having said that there were two studies done in primates the look of caloric restriction.

When did show clerk restriction extended lifespan and the other one said there was no effect. And when they compared data, they decided that the reason why there was a difference is because it wasn't a clerk in take it was how long during the day the monkeys were eating some monkeys were able to eat all day long but have a lower clerk in take the other set.

They took the food away so they can only eat for short period of time and that was just. How the study was designed and they're turned down those the ones that are eating over a short period of time. It was those [00:49:00] monkeys that actually live longer and healthier. So I do think that limiting the time during the day that you eat is going to be very important as you said because that's how we probably evolved.

Yeah, and you know again, that's why I'm such a huge fan of evolution. I get people ask me questions. And before I answer them I think about Evolution and why would we have this? Why would this be a phenomenon? Why would this is this a gift and we have just abused it and so now turning into a deficit.

When we look at things through evolutionary science we go. Oh now I get it. I see what's going on here and it's really amazing. So in summary the research that's being done right now on the dasitinib and other agents that could coincide like or certain this is actually being done with humans.

Now, you said, There were there were Phase [00:50:00] 1 and Phase 2 trials to pick on the indication that are ongoing small trials to see if there's a short-term benefit which then we'll hopefully will lead to additional studies and eventually try to see if we can slow aging very exert this really the document that these drugs will clear senescent cells from a person that has a high.

And that's in cell burden such as those that may have whole body radiation for cancer or high dose chemotherapy because of their cancer to see if we can clear these cells and if yes, then the trials will extend longer and see if we can actually slow aging but yes, there are trials currently underway and the thing that question contributes to this you said it actually suppresses the production of something that senescent cells produced that seems to cause a lot of problems well.

It targets something called pi3 kinase a certain size of form of this but we [00:51:00] don't know if that is the important targets or it could be actually the antioxidant activity in the mitochondria could be the activity. So that's been the problem, of course n because it has so many activities right? I can't tell you what it's targeting the satin of targets.

I have a spectrum of tyrosine kinases. So I know that they are important at least one of them is probably important and so they are that's there's more specificity corset and does a lot of different things. Okay. Listen, I want to thank you so much for being on the show today. Dr. Robbins.

This is fascinating and I hope that that we can keep in touch with you as new information arises we get you back on the show. So I really enjoyed that time really enjoyed talking with you. And yes, I would love to come back. Great. Take care. All right. Take care. We're going to take [00:52:00] one quick commercial break and when we come back, I got to clear something up about a show that I did last week about we were told about the ketogenic diet and we ended up stumbling on sugar alcohols and if they possibly actually convert to sugar.

And during that interview we gave a blanket all sugar alcohol seem to convert to sugar. This may not be the case. I want to talk about that when we come back stay tuned. Welcome.

So last week we did a show with Patrick Dolan from black belt nutrition. Talking about some things that happen unique things that happen in the diet as it relates to the ketogenic diet. One of the things Patrick said during the show that I wasn't prepared for it. All was that sugar alcohol turns into sugar.

I stopped them. I made him repeat it. I was like shocked because I had never heard this before apparently some of you [00:53:00] have heard it before. I had an outpouring of messages from people saying both good and bad both that this is baloney. It doesn't happen. It's BS and other people saying I've known it all along and I avoid sugar alcohols for this reason, so I don't want to I never want to go off half-cocked.

Do you know that I mean I've changed my position as I learn new things and so I started to really look into this. I'm actually asking Patrick Dolan to come back in because I asked him to research so the research that was really dumb was in 1966 and 1975 and both of these studies looked at the inhibition of fatty acid oxidation and to key and also fatty acids fatty acid conversion into ketones when fed certain sugars and Polly alcohols.

One of them was sorbitol and so these are these are. Sugar alcohols at a fairly old that have been around [00:54:00] for a long time in Fast Forward today. We have a lot of new sugar alcohols. You know xylitol is one of them more importantly Mongo sides that are found in monk fruit attend to be sugar alcohols and there's plenty of research on monk fruit that shows that it does not cause a rise in blood sugar now.

II asked Patrick Dolan to look at the research to see if they also looked at insulin because if you rise raise blood sugar just a tad but you can produce enough insulin quickly to suppress it. You may not see the spike. I'm not talking about like a big meal. I'm talking about just a little bit little rise, that could be masked.

So you have to look at basil glucose basal insulin, then the sugar alcohol is introduced. Then you have to look at the post supplementation glucose and post-implementation Insulin if glucose stays the same but insulin spikes, there's definitely [00:55:00] a metabolic changes happening the body thinks it's getting sugar.

And whether or not that small Spike of insulin could actually be the reason for the anti ketogenic response, but there are new sugar alcohols out there and one of them that's really relatively new that was introduced to the sport nutrition industry by Quest and it's called Al you lows and Al you lows while it I believe it is classified as a sugar alcohol and I could be wrong about this and we're going to find out because Patrick Darlings going to look into all this.

Paolo seems to pass through the body relatively undigested and in fact almost completely undigested. It comes in through the mouth and it goes out to the anus the same way that fact that it it moves through the body undigested would mean that it can't really have an effect on insulin or glucose.

Because the body is not getting it it's just [00:56:00] passing through it's like that piece of corn that comes out whole, you know, after you corn on the cob. It didn't affect anything. It just it just rode the train out. That's all it did. So before we put an end to this discussion about what sugar alcohol does on a metabolic level in the body.

And if it's anything to be concerned about we're going to have Patrik Dahlin back on and have him dig into some of this research on some of the newer some of the newer sugar alcohols because they've gotten more sophisticated and also like alulose they could be some that just are completely undigested.

They just pass through. So I am doing my part to clear up any questions about this because I want to know too because I use products that have sugar alcohol and I told the Lisa when we started talking about their shoes. Oh my God, you know [00:57:00] so big deal like we also have sugar in our diet right with this things that she and I eat that have sugar.

We don't avoid sugar completely now granted. It's not a large portion of our diet by any means it's very small. But if I had to start looking at sugar alcohol the same way I look at Sugar it's not going to stop me from eating the Equator the occasional dessert. Or protein bar or anything like that?

Because I don't I don't avoid sugar can put not like it so I won't buy something because it has sugar in it. I mean I eat I eat a half a bar of a 90% chocolate product. Ninety percent cocoa chocolate bar that's got almost four grams of sugar and a half a bar. I don't I don't not eat it because it's got sugar in it.

So we also need to you know deal with these kind of things [00:58:00] in a sensible manner Nothing in life is all or nothing. So, you know, we'll get to the bottom of this will do a follow-up show and we'll make sure to deliver exactly the right information because it's important to all of us. It's important to me as well.

But I wouldn't start avoiding sugar alcohols just yet. Especially if you're not on a ketogenic diet because it looks like the sugar alcohols May suppress Ketone production, but that doesn't mean anything if you're not on the ketogenic diet, if you're not looking for ketones, I mean once I break my fast I don't care if my body still producing ketones.

I'm not eating 80% fat so I could keep producing ketones. I'm eating foods that are going to spike sugar. Vegetables and starches and stuff like that. So the reality is that this discussion shouldn't matter to anybody unless maybe they're battling brain cancer and they seem to be having trouble [00:59:00] producing enough ketones.

Well, maybe they can look at sugar alcohols and see if it's having any impact on them. No Andrew Scarborough message me and said that. In his case, he avoid sugar alcohols because he's concerned about them producing sugar glucose in the blood and he's battling, you know, the he wants he never wants his brain tumor to come back.

But if you're just an average person who's choosing a protein bar as a snack because it's high protein and it turns out to have four more grams of sugar than you thought because the sugar alcohol impact you that's not a big deal. It's really not so we have to be sensible. And that's where the zealotry needs to get out of nutrition the zealotry that dictates that you eat only this way you eat only that way.

I mean there are some things to avoid but that's because of modern Agriculture and what they're contributing to [01:00:00] certain foods in the way of pesticides and so on and so forth. I'm still not a proponent. I still don't believe a little bit of chemicals is okay for you when it comes to herbicides and pesticides.

But you know, what if the sugar alcohol turns into sugar a little bit more readily? In my day, it's not going to change anything. I'm not a bodybuilder. I'm not looking to get two single-digit body fat levels. I'm looking to enjoy life while staying healthy. That's it. And that's what most of us are so don't be afraid of sugar alcohols just yet.

The jury's not out on this especially as it relates to Allie loss was like I said, are you lost passes through the body? That so it can't have any effect on you. It's like you didn't eat it at all except the taste and if sugar if glucose regulation starts at the tongue, well, maybe the body may [01:01:00] expect something sweet and squirt a little insulin out, but that's going to just make you hypoglycemic.

It's going to lower your blood sugar now, that would be an interesting thing because that means that eating a bar without a loss would be good for a diabetic. Because you're actually have the reverse effect. It would actually lower their blood sugar postprandial as opposed to raising it. How about that?

The jury's not out. We'll cover this more and tomorrow. We have a great show. Dr. Jeff Golini has a study that he's going to talk about tomorrow about how long-term adherence to a strict ketogenic diet may actually burn out the pancreas and why. This is really fascinating. This may be why people who are long-term ketogenic diet seem to stay fat or get fatter and again long-term ketogenic diets and no more appropriate for the human than long term vegan diets.

And here's the here's the reason folks vegans have [01:02:00] to supplement with different things B12 and other things because they don't get it in their. And people who are strict ketogenic diet as they have to supplement with stuff to they have to find ways to get minerals if they eating very high fat they have to take vitamins because they're not getting them in their diet any diet that requires you to supplement.

Is not appropriate for the human being for any long-term. I mean, it could be a couple months because from an evolutionary perspective you may have found yourself without any greens and having to eat a lot of fat, but usually if you're eating protein and stuff like that you're getting. Some of these vitamins through the animal through the animal flesh.

But if you're on a strict ketogenic diet, you're eating like a lot of fat you have to supplement with things that in and of itself shows that it's not appropriate because there [01:03:00] were no GN season million years ago. There were no Vitamin Shoppe two million years is no place for somebody to go. So if I'm going to be eating all this fat, I need to find minerals.

Where can I get some minerals from so. Most likely a long-term ketogenic diet would have led to nutrient deficiencies that could have either shortened or ended lives or caused disease States and Offspring. So. Once we start becoming Zealot about diet. Oh, this is the only way to eat. That's why we lose it.

I will see you tomorrow with more super human radio. Thanks for listening today.