[Garth Nicolson]: Well it’s a pleasure to be on your program.

[Damien Blenkinsopp]: To start off with, I was really interested to find out how you first started working with mitochondrial function. Where it first came up for you, and you started taking an interest in it.

[Garth Nicolson]: Well this really goes back to our work on Gulf War veterans. And from that we did work on civilians with Chronic Fatigue Syndrome, Fibromyalgia Syndrome and related fatiguing illnesses. And one of the underlying problems in all of these – and it turns out any chronic disease – is mitochondrial function. There’s just not enough energy around to provide all the necessary high energy molecules in a cell to perform all the functions necessary.

Then you get into energy deficits, and if the energy deficits are systemic, well you can have a chronic condition with lack of energy, lack of mental alertness, all kinds of other additional problems. Because basically every cell requires energy to perform. And some cells, such as the nervous system, require a lot of it – six times what most cells require – and so they’re particularly sensitive to losses in energy function.

[Damien Blenkinsopp]: It sounds like there’s a wide variety of symptoms that could be reflecting some kind of mitochondrial function damage, or interruption. Is that the case? Is it quite a wide variety of symptoms?

[Garth Nicolson]: There are a wide variety of symptoms associated with loss of mitochondrial function. And as I mentioned before, the mitochondria provide energy to your cells. In fact, almost all the energy is provided by mitochondrial function in our cells.

If you’re breathing oxygen, you’re using that oxygen to provide it to mitochondria, so they can convert it to energy, along with other molecules that they use in the process called Electron Transport System. And it’s a complicated conversion system which converts, essentially, stores that you have in your cells to high energy molecules that you need for doing a number of different functions.

Now in different clinical conditions, we find that these people have given signs and symptoms, but often they’re also related to mitochondrial function, because a lot of these problems arise when there isn’t enough energy left for cells to perform their functions necessary, and consequently this can have profound effects.

[Damien Blenkinsopp]: Right, and what kinds of damage can interfere with mitochondrial function?

[Garth Nicolson]: Well there are a variety of different types of damage. We’ve concentrated on damage to the lipid membrane of the mitochondria, because this turns out to be the most sensitive form of damage, or the most universal form of damage that we find in mitochondria. They’re particularly sensitive to oxidative damage.

And oxidative damage can occur, for example, during infection, during high performance issues, if you get run down – for example, physically, mentally, you name it – or because of infections or other damages, disease associated damages, mitochondrial function suffers. And in order to recover from all of these, you do have to have mitochondrial function available, because you can’t repair and recover without it.

[Damien Blenkinsopp]: So are we all constantly repairing the lipid membranes, as you are talking about? Is this a constant? Because when you mentioned, for instance, high performance, could that be someone like an athlete, or someone who’s heavily into fitness? Are they constantly causing this type of damage with oxidative stress, which then has to be repaired?

[Garth Nicolson]: Well, that’s true, but it’s also true during aging, for example, where our membranes normally get damaged during aging processes. And mitochondrial membranes are particularly sensitive to aging, and as we age, they get more damaged. And so if you look at a 90 year old, many of these 90 plus year old people have lost almost half their mitochondrial function.

And a lot of that is due to accumulated damage in the mitochondria, and a lot of the damage is due to the damage to the mitochondrial membrane. And the inner mitochondrial membrane is integral to our production of energy, and if that’s damaged, they become leaky, and lose function, and they can’t maintain the trans-membrane potential, the electrical potential across the inner mitochondrial membrane, which is absolutely necessary to produce high energy molecules.

[Damien Blenkinsopp]: Right, right. Well to take a step back, when you’re talking about trans-membrane, what’s the function of the membrane in terms of generating electricity? Because basically the mitochondria are a bit like our power cells, you know our batteries, which feed our cells and the rest of our body with energy. But how do they do that, and what’s the role of the membrane in that process?

[Garth Nicolson]: Well I always liken mitochondria to the little batteries inside our cells. And like any battery, it has to be insulated to selectively permit a trans-membrane potential across different membranes in our mitochondria. It’s a biological membrane instead of a synthetic membrane that we have in batteries, but it provides the same kind of insulation necessary to separate electrical charges.

And so when this separation of electrical charges occurs, you can make a battery out of it. Essentially that battery drives the production of high energy molecules in the mitochondria just as it does in a normal battery.

[Damien Blenkinsopp]: Great. And what types of damage are we talking about when we’re talking about this membrane getting damaged?

[Garth Nicolson]: Well there’s certain molecules in the membrane. It can be the phospholipids that make up the matrix of the membrane. But when they’re damaged, there can be enhanced leakiness across the membrane. So it’s like you get a leakiness if you take the insulation off a battery it will leak, and you’ll lose the charge of the battery.

The same thing in the mitochondria. If they become leaky, and the inner membrane becomes leaky, you can lose the trans-membrane potential, and then you can’t form the high energy molecules. There are also some critical lipid molecules, like cardiolipin, that are exquisitely sensitive, in fact, to oxidative damage. And when they’re damaged, this results in loss of function. So these different types of things are very important, the direct function and the trans-membrane potential.

[Damien Blenkinsopp]: So these are different types of fat molecules that we need in the membrane for it to function optimally. And it’s kind of like holes have been punched in the surface of the membrane, and molecules have been knocked out of it? Is that a way to look at it?

[Garth Nicolson]: It’s a little more subtle than that. When oxidative damage occurs, think of the lipid chains that are going into the membrane, into the hydrophobic matrix of the membrane, you can think of kinks getting in those chains after they’ve been oxidatively damaged. And those kinks mean that the lipids can’t fit together as well, and there’s a certain rate of leakiness across the membrane.

[Damien Blenkinsopp]: Great. Is this something anyone should be concerned about, in terms of the type of damage? You just referred to a 90 year old, the damage that’s gone on to them.

What kind if symptoms could someone think of if, maybe they don’t have a chronic disease like some of the ones you referred to, but are there other indicators that potentially they have some aspect of mitochondrial damage, in terms of some symptoms they could look out for which might identify that?

You were referring to, like brain fog, or other symptoms. Are there obvious ones, or is it always very different, and it’s kind of difficult to differentiate this to other things that might be going on?

[Garth Nicolson]: Well, obviously a number of different factors can cause problems with your central nervous system, for example, your peripheral nerves and other systems of your cells, but one of the things that can happen is that if the energy systems inside the cells get run down, they don’t function as well. It’s as simple as that.

So if you don’t produce enough energy in your cells, your cells can’t function as well. So all the different functions that cells do, of course the nervous system, the function is to transmit nerve impulses, if they’re not functioning properly then the nerve impulses can’t be transmitted properly. And so that leads to a loss of function.

Now this can occur when people get run down. And they can get run down for a variety of reasons. They can lose their energy stores, for example, or they can have them damaged through the mitochondrial damage that I was talking about. Some of this occurs naturally, and it’s reversed by rebuilding things like the membrane as it’s damaged.

And if there’s some process that prevents that rebuilding of the membrane, then this will persist. For example, during infection we know that a variety of different types of infections – viral, bacterial and so on – cause an increase in the what are called reactive oxygen species, or ROS. And these damage the membranes of the cell, and in particular they can damage the inner mitochondrial membrane and cause loss of function.

So these are things that can happen. So it can happen during infection, it can happen during aging, it can happen during a chronic illness. It can happen when you get run down, for example, or you have exposures of various types that are toxic. So under a variety of different conditions you can have damage done to your mitochondria, which means loss of function, and your body cannot repair itself as well without that energy that’s necessary to do it.

[Damien Blenkinsopp]: Great. And I guess an important differentiation I just wanted to point out here is a lot of people talk about adrenal fatigue, and if one of the symptoms is fatigue, basically having low energy – which I guess would be one of the outputs of mitochondrial damage – how do you differentiate it, or is it possible to differentiate it, to something which someone would diagnose as adrenal fatigue? Or how do you look at that?

[Garth Nicolson]: Well they go hand in hand, because for the adrenal gland to function, it requires energy. So if there’s an energy deficit in the adrenal gland, then that’s not producing the correct hormones and everything that your body needs. Cytokines and so on. So this sends up the deficit, and this can cause a problem. So they’re inter-related.

[Damien Blenkinsopp]: Right, right. And it sounds like you’d think mitochondrial damage might be a pre-cursor to adrenal fatigue, often.

[Garth Nicolson]: It could be a pre-cursor to adrenal fatigue. And so we’ve seen people that have managed to repair their endocrine systems by repairing their mitochondria. So at least we know, and at least in some patients, that’s reversible.

Now in other patients they may have either genetic defects, or toxic exposures, or something like that, that’s damaging specifically those particular adrenal glands. So that’s a different issue. But we do know that these things are inter-related. If you don’t have the energy, you can’t repair.

[Damien Blenkinsopp]: So you’ve worked, in your clinical studies and your patient population, you’ve worked with Gulf War illness and Chronic Fatigue Syndrome and some others. Could you give us a brief explanation, for the audience, what are the issues that these people have? How critical are they, what kind of situation are they in? Before we talk about the lipid replacement therapy and what it was able to do.

[Garth Nicolson]: Well there’s quite a bit of variation on the signs and symptoms of people with chronic illnesses, and a variety of different sorts. We started working with what are called Fatiguing illnesses, because Chronic Fatigue is the hallmark of those illnesses, and that’s directly related to mitochondrial function. So that was a good place to start.

A lot of other diseases, mitochondrial function may be thought of as a side issue; although it’s important it may not be the primary clinical manifestation of the disease process. Nonetheless, it’s still important [for] practically any chronic illness.

If you take something like a neurodegenerative disease, for example, mitochondrial function is intimately tied up with neurodegeneration. You cannot repair your nervous system if you don’t have the energy available to do it. So if mitochondrial function goes down, you’re particularly susceptible to neural damage. And to have that process going on, it can exacerbate it.

So this is one of the things that we are trying to work with, how to improve mitochondrial function, how to help people with a variety of chronic illnesses.

So we started with the fatiguing illnesses, and Gulf War Illnesses are really one of the fatiguing illnesses, but Chronic Fatigue Syndrome is another one, Fibromyalgia syndrome is another. Fibromyalgia syndrome is a little different because it’s also characterized by widespread pain, in part, we think, that’s due to mitochondrial function problems as well. The nervous system not operating properly. But there are some other factors as well.

So all these issues have as an underlying commonality loss of mitochondrial function. In a variety of different diseases, that’s true. And it’s true in infections, it’s true in toxic exposures, it’s true in a wide variety of different diseases. Cancer, you name it, practically every disease you can think of has a problem with mitochondrial function. They can’t keep up the repair process.

[Damien Blenkinsopp]: Are there other, beyond the ones we’ve already discussed, are there other types of patient populations, or other use cases you’ve looked at for lipid replacement therapy? You mentioned anti-aging as well. Have you worked with people for that area also?

[Garth Nicolson]: Exactly. Well, anti-aging is probably the normal manifestation of mitochondrial functions. I mentioned as you age you lose mitochondrial function naturally. And there’s an increase in the oxidative damage that occurs in all of our cells, so we need to reverse that process.

And so, one of the things we’ve done with the aging process is we’ve taken people that were fatigued, 90 years old plus, we’ve improved their mitochondrial function to a 30 year old. And they’ve gained all kinds of function in the process. Mental function, physical function, you name it. Every system that seems to be important improves.

[Damien Blenkinsopp]: In terms of the studies you’ve done, are these all based on studies, or is some of this based on patient population, other studies? Because I’ve seen some of your presentations, looking at your studies and work on the fatigue cases and the Gulf War Syndrome. So are all of the studies basically based on those patient populations versus the anti-aging, or have you also done studies on anti-aging also?

[Garth Nicolson]: Well we’ve done some studies where we’ve included older people in our studies, and that’s where we see the anti-aging effect. So with those older cohorts of patients – well they really are, they’re subjects, not patients, because their main problem is they’re elderly and they have fatigue issues. So we can’t categorize them as a disease process, because it’s a natural process of aging.

So they are fatigue subjects. So they have chronic fatigue, but they don’t have a disease called Chronic Fatigue syndrome, or Myalgic Encephalopathy, or something like that. They have fatigue problems. So we work with people like that as well.

We’ve also worked with cancer patients, we’ve worked with people with chemical exposures, we’ve worked with people with infections. For example, there are a wide variety of chronic infections that we work with, like Lyme disease, mycoplasma infection, so on and so forth. Were, again, in the chronic disease process, it’s always an issue. Mitochondrial function is always an issue.

[Damien Blenkinsopp]: Right. Would you say it’s going to be helpful in most situations to have some kind of lipid replacement therapy as a support for your mitochondria? In terms of the disease process, to give an idea, what kind of results do you get from people? Can you get people back to resolution? Or is this basically managing symptoms, managing the damage of mitochondria, kind of therapy?

[Garth Nicolson]: Well it depends on the situation. If we take normal, healthy people that can get run down for one reason or another, yes we can bring them completely back by repairing their mitochondrial function.

If you take people that are in a disease process, usually these processes are much more complex than just mitochondrial function. Mitochondria being one part of the problem that they have. And we can repair that part, but there are other elements that have to be taken care of as well. For example, if you take somebody with a neurodegenerative disease, does just repairing their mitochondria reverse the process? No. There’s some other elements that are involved.

Does it help? Yes, it seems to help people with cognitive loss and so on and so forth. But it doesn’t reverse it or completely cure the problem. That would be a pretty simplistic approach to these complex, multi-factorial issues. But, we do know that this is an important element in all of these processes.

[Damien Blenkinsopp]: Do you feel like it provides a support to get people to recovery? That it’s an important ingredient in your practice? You feel like it helps people to recover by giving them that mitochondria energy, thus supporting things like the immune system, and other systems of the body?

[Garth Nicolson]: Absolutely. If you’re talking about the immune system, for example, it requires energy to function. So if your energy goes down, your system might be less capable. So, it’s absolutely important there.

And it’s absolutely important for any type of recovery, because what is recovery? Generally it’s repairing our cellular processes and our system processes, our organ processes, and that requires energy. That just doesn’t happen naturally without energy.

[Damien Blenkinsopp]: Okay, so let’s get kind of concrete here, for the audience listening at home. What is lipid replacement therapy? What does that actually involve, what do people do when they’re taking lipid replacement therapy?

[Garth Nicolson]: Well this is a particular type of lipid, this is not just the normal gross lipids that people might think of. These are very particular membrane lipids, so these are lipids that make up the membranes of all our cells. And of course as I mentioned before the membrane is an integral part of the mitochondria, but they’re also an integral part of other organelles within the cell.

Membranes, in fact, are absolutely essential for the function of all of our cells. And they get damaged, they get run down, we have to replace the molecules and the membrane occasionally. And some of the most sensitive molecules are the lipid molecules, because they’re very sensitive to oxidative damage, which can occur in any disease process, infection, or whatever.

So this is something that has to be replaced. And we came up with this idea, well we need to replace the membrane lipids, which are primarily a class of lipids called glycerophospholipids, that don’t need a lot of other things. That’s what we need to help repair the, more or less the matrix of the membrane.

So if we supply that in purified form, undamaged form – which is very important – then we should be able to help repair this process, because we have natural systems in our body to replace these lipids as they’re damaged. Because we evolved with the mechanism to help repair and replenish our membranes.
The problem is we can’t keep with the damage, and that’s when the disease process can occur. So to help it along, if we provide the lipids, well we can help that process.

Now people say well, you can buy all kinds of different stuff at the store. Well, the reason it doesn’t do it is a lot of those lipids are already damaged, they’re already oxidized, they’re not the right kind of lipids, and so on. So they’re not very helpful. And even a lot of supplements that people buy in the store are not very helpful, because even if they have lipids they’re not the right kind of lipids, or they’re already damaged, or they’re damaged during the shelf-life.

These are very sensitive issues, which we’ve tried to overcome with the products that are designed to survive and provide our bodies with exactly the right lipids that we need to repair our membranes and restore function.

[Damien Blenkinsopp]: So, would it be correct to, because you provide these in pill form. So is it these are things we can get from food, but we get them in very low quantities, so it’s like having a very high dose of the reduced form? The active form versus the oxidized form of these lipids?

[Garth Nicolson]: Well that’s part of it, but a lot of the lipids are damaged already by the time we take then in in the foods, and unfortunately, our transport systems, they can’t readily acknowledge a damaged lipid from a properly pristine, undamaged lipid. And so a lot of these things might get transported in as well. Or at least they’re transported in, too much of it is transported in if it’s damaged.

So we kind of flood the system with undamaged lipids, and that helps the whole process move very smoothly. It also helps remove the damaged lipids, which is one thing we’re working on now, is how to take people who are chemically damaged – and I can talk about that later – help them remove those damaged chemicals from their bodies.

And it turns out that the replacement therapy can help do that, because it’s an energy driven process, so it helps provide energy, but it also is very dependent upon moving what we call hydrophobic molecules out of the cells. And the lipids that we provide have a very important part of their structure, a hydrophobic part of their structure, which helps remove these molecules.

So if they’re present in quite a bit of excess it can help remove these damaging chemicals from our system. And that’s one thing we’re working on right now.

[Damien Blenkinsopp]: That sounds very interesting. We’ve spoken about detoxification before. So, just to take a step back, when you say chemically damaged people, what kind of things has happened to these people?

[Garth Nicolson]: Well often people with chemical damage due to illness could be anything from herbicides, for example, to very industrial chemicals, and so on and so forth. Often damaging chemicals are chemicals that we would classify as hydrophobic chemicals. That is, they don’t like water. They like fat, essentially.

So they concentrate in our membranes, they concentrate in the fatty parts of our cells and lipid droplets, and so on. And they can remain there indefinitely. And they can bleed out very slowly and cause problems with the cellular mechanisms. So to get rid of these, we need a system to remove them.

But the system that we have for detoxification is an energy dependent system, at least one of the most important ones. So by providing mitochondrial energy, that helps in that process. But it also helps remove them because, it turns out, the lipids that we provide kind of soak up these molecules, because it will bind to the lipids and it helps them be excreted from our cells and from our system, so they naturally come out in the GI system.

[Damien Blenkinsopp]: So that sounds like the new molecules that you’re providing are basically replacing the ones which have absorbed the toxins, the chemicals, the fat soluble chemicals, and are thereby displacing them and allowing the body to remove them.

[Garth Nicolson]: Well that’s basically it, but it’s providing a different store, or different storehouse for these chemicals to move into, but a storehouse that we can eliminate. And that’s the important thing is to do that.

One of the mechanisms for moving chemicals that’s most important for these very damaging chemicals that concentrate in our cells is that there are enzymatic mechanisms, to conjugate the offending chemicals with other hydrophobic molecules within the cells, to make them more easily removable.

Well when that happens, if we have somebody’s undergoing lipid replacement therapy, there are a lot of these lipid droplets around and lipid carriers around, which could help soak these conjugated chemicals up and remove them from our systems.

So it’s a process, it’s a very slow and steady process of removal. It doesn’t, of course, happen over night, but it’s a natural system for removal of damaging offending chemicals from our bodies. And this just takes it to a maximum advantage by providing some of the things necessary for it to operate in the first place.

[Damien Blenkinsopp]: So out of interest, because we’ve spoken quite a bit about detoxification, and also the kinds of tests involved in measuring things like mercury, lead, and other toxins. Are you able to test these chemicals in fats and see the change, and how long does it take? Does it take a month, two months?

[Garth Nicolson]: Again, we’re not talking about heavy metals, because that’s a different process of removal. We’re talking about chemicals that partition themselves into the fatty portions of your cells. Well these chemicals, and they could be, for example, herbicides or any number of different chemicals.

[Garth Nicolson]: Yeah, a lot of the chemicals that damage our cells are very hydrophobic, and they partition into the fats of the cell, the fat systems and the membranes of the cell. They have to be removed or eventually they’ll interfere with the function. That removal process is slow. It does not happen over night.

So it’s a very slow process of bleeding them out and removing them from the stores, and so on and so forth. So one of the first things that you can see, for example, if you give somebody lipid replacement therapy, is you might actually see an increase in the number of these chemicals that are being excreted, that are being at least mobilized as well.

So there may be an increase in the blood levels of these, because they’re being brought out of the cells and being transported to the brush border cells in the intestines, and then secreted there. But again, there are a number of different mechanisms, this being just one of them.

[Damien Blenkinsopp]: I’m guessing this is a new area, it sounds like you’re more focused on this recently?

[Garth Nicolson]: This is a very new area of ours that we planned to get very focused on because it’s so important, so necessary to help these people, many of whom have been damaged for decades without much help at all.

[Damien Blenkinsopp]: So just out of interest, are there any specific exposures? And is it people working in factories, or is it people who have detoxification systems which aren’t functioning, or perhaps they have some methylation or other issues, which they’ve lived a pretty normal life, compared to most people. It’s not like they’ve been in any specific situation which could have exposed them to more chemicals.

What kind of populations are you dealing with here?

[Garth Nicolson]: We work with the populations that are sick in general, although a variety of different individuals may be exposed to chemicals, because they are all over the place in our modern environment. And people will have tremendous variation in their sensitivities to these chemicals.

So you may have somebody that’s been normally and naturally exposed who’s becoming sick because of it, and other people not at all. Because there’s such a range of sensitivities to these.

So we’ve worked with people who’ve had specific exposure. For example Vietnam war veterans who’ve had exposure to Agent Orange, which is a particularly nasty chemical that takes a long time to remove from the body. Or Gulf War veterans that are exposed to petrochemicals in the forms of fumes, and exhausts, and oil fires, and so on and so forth, during the first Gulf War, and some during the second Gulf War.

So these are people that have had chemical exposures above and beyond the normal types of exposures that we might see. But in the industrial environment that we’re in, there are a lot of people that get exposed to various chemicals.

If you work in the petrol-chemical industry, for example, you could be exposed fairly easily, and it may not cause any problems with you but there are other individuals who have severe problems because of it.

So again, there’s a wide range of different sensitivities to these different chemicals that are seemingly in our population.

[Damien Blenkinsopp]: Great. I just want to bring it up, because I know a lot of people talk about infrared saunas, and saunas in general when it comes to fat detoxing from the fat soluble toxins like the ones we’re talking about. So, do you have a viewpoint on that, on the effectiveness of infrared sauna? Is it something you’ve ever gotten involved with, and could you compare it to your process?

[Garth Nicolson]: We’ve looked a bit into that, and yes the use of infrared saunas to actually bring the chemicals out in your sweat, which is what it really does. But if you do these at least a minimum two times a week, you’ll slowly start to deplete some of the chemicals from your body.

What we found is if you add our lipid replacement therapy on top of that, you can accelerate the process of removing the chemicals from your body that way. So again, this can be an adjunct to a variety of very well established methods for detoxification.

[Damien Blenkinsopp]: Great. Have you seen complete recoveries, or to what degree have people recovered from their health? Because we’re talking about people that are quite sick.

[Garth Nicolson]: Well, we’re in the beginning process of this right now. So this long term goal of ours, but again, this is just the beginning, and we’re seeing some responses. We’re seeing people that are feeling better, getting better. But again, it’s a long, slow process for recovery.

And again, there may be other types of damage along the way that we discover that these individuals have. Most of these chronic illnesses are multi-factorial. There’s not just one problem, generally these people have a number of problems, this being one of them. But this is something that we can approach.

[Damien Blenkinsopp]: Absolutely. So it sounds like an on-going process of a year. We’re talking really long term, just to give people an idea.

[Garth Nicolson]: We’re talking long term. Particularly when it comes to removing offending chemicals from your body, it’s a long term process. Same thing with removal of heavy metals from your body, it’s not a short term process.

It can take years to remove heavy metals from your body, and the same thing is true with chemicals that build up in your body. It can take a long time to really get rid of them. And in fact, if you mobilize them too quickly, you can really make people feel sick in the process. So it’s better to do it naturally and slowly.

[Damien Blenkinsopp]: So, I’m glad you brought this up, because we’ve spoken about these kind of topics quite often on the podcast before. It’s nice to get that. Is there anything you have to do in terms of supporting them?

Because you mentioned that some people can get sick if it comes up too fast. Is there anything else that you do for them while you’re using the lipid replacement therapy to support detox, or as long as you go at a reasonable rate, which I imagine is a reasonable dose?

[Garth Nicolson]: What we have found is that lipid replacement therapy actually reduces the symptoms of detoxification, reduces the symptoms, for example, of cancer chemotherapy. So it is very significant in our studies with the cancer patients. They’ve showed really quite a dramatic decrease in the side effects due to chemotherapy, because it causes a lot of damage to our normal systems, and the lipid replacement therapy helps repair those normal systems.

So you get a reduction in the associate problems, very adverse events that occur during cancer therapies. So, you could figure that is, again, when you’re repairing the normal mechanisms of the cells, the tissues, and this helps the overall process.

[Damien Blenkinsopp]: Right, right. So you’re saying a lot of the symptoms people have when they’re going to a detoxification process, or, as you’re saying, chemotherapy or exposure to other toxins or when they’re ill, is due to mitochondrial damage, right?

So when you’re supporting the mitochondria with lipid replacement therapy, it helps to manage the symptoms as well in that process and reduce them, because there’s not as much damage going on.

[Garth Nicolson]: Well it does, and not only that, it helps accessory systems as well, because a lot of the signs and symptoms that we see that are associated with damage are release of chemical messengers like cytokines, that cause all kinds of problems in the body, and so on.

And damaged tissues can initiate this whole process. So if you reduce the damage, you can reduce these accessory damage response systems from exacerbating the signs and symptoms in these patients.

[Damien Blenkinsopp]: Great. One thing I wanted to kind of make clear to people, what kind of results, because when I was watching some of your clinical studies you were looking at. Over the few months you were giving lipid replacement therapy, could you talk about what kind of impacts it generally has on the people?

If we’re talking about say the chronic fatigue, or in the Gulf Syndrome cases, the ones I saw, what kind of time-lines did you walk through in your clinical studies? And also, it was interesting what happens when you stopped the therapy.

[Garth Nicolson]: This is a process that takes time. You don’t repair your mitochondria overnight. It takes days to weeks. The process can begin fairly soon after you take the lipid replacement, but it takes time to fully repair the mitochondria.

And we’ve seen, again, that it can take, depending upon the different formulations of lipids, anywhere from 10 days to three months, depending on the formulation, depending on the patient type, to reach an equilibrium of repair. And these people see a maximum benefit in that time. But they do see benefit fairly, fairly soon.

[Damien Blenkinsopp]: And then what happens when you stop the therapy? Depending on the condition. So when it’s in a chronic condition, like Chronic Fatigue Syndrome, or Gulf Syndrome, where they have some kind of infection or some underlying cause, then what happens when you stop the therapy?

[Garth Nicolson]: Well then it slowly returns back. As the mitochondria get damaged again, it will slowly go back to the way it was before you started the therapy. And one of the trials that we did was called a cross-over trial, where we take patients, and they’re on part placebo and part the lipid replacement therapy, but they don’t know when they get it.

And what we found was when they get the lipid replacement therapy, they improved. They had reductions in fatigue with 35 to 45%, enhancement of mitochondrial function was a little bit less than that in terms of percentage, but very significant. But when we switched them to placebo, it slowly started to go back again.

[Damien Blenkinsopp]: Yeah.

[Garth Nicolson]: And they wondered what was going on, because it wasn’t having the same effect. So we could prove that it was in fact the lipid replacement therapy that was giving them the benefit, not a placebo effect.

[Damien Blenkinsopp]: Great, thank you very much for that. And so, what were you using to assess mitochondrial function in terms of tests?

[Garth Nicolson]: Well what we do is we take a blood sample from patients, we isolate the white blood cells which have mitochondria – the red blood cells do not have mitochondria – and we can measure the mitochondrial function directly.

And what we’ve done actually, more recently, is we’ve measured the membrane potential of the inner mitochondrial membrane using a special redox dye, called rhodamine 123, and see that fluorescent dye in the mitochondria. If the mitochondria are fully functioning, they will reduce that dye and it will fluoresce.

And if they’re not functioning, they can’t reduce it, and the mitochondria won’t fluoresce. So you can see it visually in a microscope and you can quantitate the fluorescence so we can get a quantitative value.

[Damien Blenkinsopp]: Great, great. So this is your own lab tests that you developed for this purpose?

[Garth Nicolson]: Well other people really developed the tests, we just adapted it to what we were doing.

[Damien Blenkinsopp]: Great. Well I guess what I wanted to say is it’s a pretty unique [test], like we wouldn’t expect to find it outside of research, apart from potentially your practice, and some other specific areas.

[Garth Nicolson]: This is a very specific research type of test, and you won’t find it in your normal doctors office, that’s for sure. Because it requires some complicated machinery, like a cell sorter and fluorescent tools, fluorescent light sources, and so on and so forth. So, it’s a bit complicated, but it works in a research environment.

[Damien Blenkinsopp]: So it’s not something you use on your patient population, I guess it’s cost prohibitive. It sounds like quite complex.

[Garth Nicolson]: Well it is, and speed is very important. So you have to have a very fresh sample. Often if you’re not doing the test immediately or soon, you could get variable results. So to get the best results, speed is very important. So, generally you have to have this complicated equipment on hand to do it. And the technical expertise to do it.

[Damien Blenkinsopp]: So, how well accepted is lipid replacement therapy? We’ve spoken with functional medicine doctors here, and we’ve looked at functional medicine quite a bit, contemporary medicine is there of course also, and in the research studies.

Is there a lot of support for it right now, or is it still something quite niche that basically there’s not very many people using?

[Garth Nicolson]: Well more and more are using it, because more and more people are finding out about it. And we published some 28 papers on this process. So, it’s well-known in the literature. We published a number of reviews on it now.

Less known in the general population of physicians, more in the naturopathic medicine areas, mainly because I get around and talk to these people, and then they get informed that way, through conferences and so on. So it’s becoming more and more well-known, and even people outside the medical area will find out about it through broadcasts like yours, for example.

They can buy this stuff over the counter, it’s not something they need their physician’s prescription for. These are natural supplements. It’s the lipids that are in our membranes all along. So, it’s not a drug, it’s not anything but what’s there. We just have to provide it in a way that’s not damaged.

[Damien Blenkinsopp]: Well so I’ve got to ask you the question, are you using lipid replacement therapy yourself?

[Garth Nicolson]: Absolutely.

[Damien Blenkinsopp]: Okay. How long have you been using it?

[Garth Nicolson]: Well, I’ve been using it for years now. It was very effective for me in terms of reduction of fatigue. And for example, recently I got an influenza virus, unfortunately. It kind of knocked me down, and this helped the repair process. I recovered much more quickly than normal, and so I think it’s very useful for that.

[Damien Blenkinsopp]: What kind of dose are you taking? Let’s talk about practicals here. Because I’m taking ATP Fuel, for example, because I’ve had my own issues and it was recommended to me. And your research was recommended to me, so that’s kind of where I came into it.

So I’ve been taking that for a while, the ATP Fuel. And you have the NT Factor, which is a part of that. Is that actually your company who supplies that, or is that another company?

[Garth Nicolson]: I’m in a non-profit organization. We’re not really a company, but we do consult with companies like Researched Nutritionals that makes the ATP Fuel, [and] Nutritional Therapeutics in New York which makes the NT Factor, the lipids.

In fact, the Researched Nutritionals uses the NT factor product in their own product. They add some other things as well. So, ATP Fuel is an excellent product for these chemical exposure patients. In fact, I’ve just been going back and forth with the President of Research Nutritionals because we need to increase the amount of NT Factor, which is the lipids, to that product to really help these individuals.

So what we found is that more of the NT Factor is actually better. You might want to supplement your ATP Fuel with some NT Factor Lipid Wafers. By the way this is an excellent product.

We use these with children, for example, that have autism spectrum disorders, and these children have mitochondrial function problems. They readily take these wafers, and they don’t take pills. You can’t get them to take a pill.

[Damien Blenkinsopp]: Right, right.

[Garth Nicolson]: But these wafers are very tasty, and they’re creamy, they melt in your mouth because they’re lipids. So they like these creamy things, and so we have no problem with the compliance, even with difficult cases like these autistic children.

These are things that we work with on a daily basis, and we’re trying to improve our products as we go. Recently we found that although ATP Fuel is a really good product, I’m saying for the chemically exposed individuals that we need to increase the amount of NT Factor with the lipids in that product.

[Damien Blenkinsopp]: So just for the audience, the ATP Fuel has co-enzyme 10 and NADH added to it. Obviously, say that the dose of the lipids, which you say is the most important, this is kind of the innovation here, the lipid replacement therapy.

[Garth Nicolson]: That seems to be the most important thing because if you leave that out, it’s not very effective. If you put it in, it’s very effective. So it is a combination, but it’s a critical part of that combination.

[Damien Blenkinsopp]: Let’s just talk downsides here. Are there any downsides you know to this, and are there any safety issues? I just want to make that clear in terms of, maybe if you overdose it. You’re talking about increasing a dose for chemically exposed people. Is there any downside or risk to taking a lot of this?

[Garth Nicolson]: We’ve never seen any safety issues with the NT Factor lipids. As a matter of fact, we’ve given approximately 40,000,000 doses of this to patients without any recorded evidence of a real side effect.

And the reason for that is these are natural molecules that are in our cells and our systems all along. So we’re not giving our systems anything that’s different. We’re not giving them a drug, we’re not giving them something that they don’t see all the time anyway. I don’t know that it has any toxicity.

There are some studies that had been done in animals, where they’ve been given tremendous doses, without any effect at all. And we’ve had patients that have been on, oh, up to several grams per day of the NT Factor lipids without any [negative], as a matter of fact more positive effects. Their blood lipids had more normalized, they’ve had a lot of really positive things happen to them.

[Damien Blenkinsopp]: So that’s interesting. What kind of quantitative changes have you seen in terms of, are you talking about cholesterol markers?

[Garth Nicolson]: Yes.

[Damien Blenkinsopp]: Have those changed as well?

[Garth Nicolson]: Cholesterol markers and bad and good lipids. For example, lipoproteins, we’ve seen a move in the right direction. We’ve seen reductions in a product that’s associated with Heart Disease, homocysteine.

We’ve seen in elderly patients a reduction over time in homocysteine levels, which are directly related to coronary, artery disease and heart attack. So these are some of the beneficial things that we’ve seen in patients taking this long term.

[Damien Blenkinsopp]: Great, great, thank you for that. So, are there things that you’re looking for in the next five or ten years, where you think there’s going to be some more changes or innovation? Or is there anything you’re kind of excited about the opportunity of this, to help more people or to improve it?

[Garth Nicolson]: Well we’re doing an anti-aging study right now, which I’m very excited about. It’s actually going on in Uruguay. A colleague of mine who is there is a specialist on sperm function, and he takes care of men with fertility problems. But as we age, our sperm function declines, and that’s what I’m interested in as a test model for anti-aging.

So far what we’ve seen is that even in vitro, if you take sperm they have a certain lifetime. So if you take older men they have less of a lifetime, that is they can be for a while, but then they start losing motility more rapidly than younger men. But if we put in the NT Factor in it, we can help restore the function of the sperm even from older men.

So the next step is that we’re going to go from these in vitro experiments, which are very interesting, sperm motility, to in vivo experiments where we look at actual men with fertility problems that have functional problems with their sperm motility, and see if we can help repair that process.

But in terms of it’s anti-aging, which is what I’m really looking for, long range, this is an interesting model to look at. So whenever we have systems that undergo slow degeneration, like sperm function over time, if we can reverse that process, that means that we’re having an anti-aging effect, and it’s very clear, it’s very specific, and very quantitative effect. And so that’s one of the systems that we’re looking at, and I’m very excited about.

And we also have a number of different diseases processes that we’re very interested in, and we’re trying to intervene and see if we can help. Neurodegenerative diseases is one thing I’m very interested in. That’s obviously a very long term and slow process to eventually recruit patients in that area.

Another thing is reducing the adverse effects of cancer in cancer therapy. So there are two aspects of this. If some person has cancer, often they have what’s known as cancer associated fatigue, in the absence of any therapy. And of course the NT Factor will help patients with that.

We’ve seen a 30% reduction in that fatigue with patients with long-term cancer, that have had cancer associated fatigue. But it’s really reducing the side effects of cancer therapy that is most interesting, because we’ve seen reductions in side effects to chemotherapy that are really dramatic. So there’s reductions, for example, not only in fatigue but in vomiting, and malaise, and a number of other side effects – headaches, for example, and so on – associated with chemotherapy.

I think the reason for that is we’re helping repair the normal systems very rapidly in these patients after their burst of chemotherapy. So you might ask, well does this interfere with the therapy? And the answer is no, because it turns out there’s a window of therapy which is very short for the cancer, but it’s very long for the normal systems.

So these chemotherapeutic drugs attack the cancer very quickly, but then they have lingering effects on our normal systems for months, literally, after the therapy is over. So, what this does is the NT Factor helps reverse that process of damage after the therapy.

[Damien Blenkinsopp]: It sounds like you’re saying that there’s no risk of them providing a protective effect to the cancer cells themselves, provided that you introduce a timing?

[Garth Nicolson]: Well what we do is we put it in after the therapy. Because we know the damage to the cancer cells occurs very quickly. Generally, within hours after the therapy is administered. Whereas the damage to the normal systems occurs for weeks, or even months later. So we allow the therapy to occur and then next day, the following day, we start the lipid replacement to help repair the normal systems.

[Damien Blenkinsopp]: This is really interesting work. You must be really excited about all of these projects you’ve been working on.

[Garth Nicolson]: There’s something new every day!

[Damien Blenkinsopp]: And luckily you have lipid replacement therapy to keep your energy up, so you can keep focused on them all.

[Garth Nicolson]: Well I’m taking it, and so far it’s been a real help. I know that personally. But every individual will have to see what’s optimal for them. Some people will find they have to take a bit more of the lipid replacement than other people, and that may have to do with their transport systems that bring these lipids into their bodies and cells, and everybody’s different in that regard as well.

So, the same thing with detoxification. We have systems in place to help detoxify us, but it’s working so poorly for most people, or their systems are swamped out with these dangerous chemicals and they can’t keep up with the damage, and so this helps accelerate the removal of chemicals.

And also, we know that’s an energy dependent process. So it helps rebuild the energy systems that are necessary for detoxification. Because detoxification just doesn’t occur naturally, it requires energy.

So if you don’t have the cellular energy necessary, you can give them all kinds of different things, and you’re not going to see much improvement, or at least you could see much better improvement if you repair their energy systems at the same time. So I think for any detoxification, mitochondrial repair is really important, because it really helps accelerate the detoxification process.

[Damien Blenkinsopp]: Great, great, thank you. There is a cost side of this kind of therapy.

So, in terms of monitoring, how do you assess whether someone should remain on the treatment? Is it purely based on symptoms resolution, or whatever they’re trying to achieve, or do you have any markers? You brought up the homocysteine, for example. So if they had raised homocysteine and it leveled out, you could say, okay now I can take you off the therapy, because you’ve got to that critical [point].

[Garth Nicolson]: Well, actually, here’s the problem that we have in the modern environment. We don’t stop people from being exposed. We don’t stop people from getting sick, we don’t stop people from getting into automobile accidents, or whatever. We can’t do that, but what we can help them do is repair once it occurs.

We can help repair and accelerate the healing process due to trauma. We can help the healing process due to infection. We can help the process due to long term treatment of a chronic condition. All of that means that this is a long term solution, not a quick fix. And that’s why I’m taking this for the rest of my life.

And I put my father on it when he was 92, and he had much better cognition, he had less fatigue issues, and was more ambulatory, and clearer thinking, and so on and so forth. And he lived another eight or nine years. He was a coronary patient and he was on his last legs when he started.

So I think it’s never too soon. Just like it’s never too soon to stop smoking, it’s never too soon to start taking lipid replacement therapy. And yes, you may have to take it for the rest of your life if you want the benefit.

[Damien Blenkinsopp]: Well, I think I’m certainly going to stay on it. And I’m very glad to have you on the show to spread the information about this. It’s been very useful to me.

In terms of other people who, besides yourself, you would recommend to talk to about mitochondria, or lipid replacement therapy. Is there anyone else who’s done work which you would reference which is interesting, that have done a lot of work in this area?

[Garth Nicolson]: People can go to our publications, because they can see what we’ve cited in terms of the references, and the groups, and so on. Yes, there are other people working on different aspects of it. For example, there are some groups in Europe that are using intravenous lipids – similar type but not the same – and they’re getting very good results with that.

We prefer the oral supplements because obviously you can’t go in every day for an intravenous lipid replacement therapy. So, we prefer people take it orally, because we know we have the mechanism in our brush border cells lining our guts to bring these lipids in naturally, because they’re essential lipids. So, this is a very natural process that we’re supplementing, essentially.

And I think people need to find out about this. The ATP Fuel that you mentioned is primarily available through physicians and naturopaths, and professional health people, but there are also a lot of people out there maybe listening that want to know where can I get this stuff on my own.

And there’s a website called NTFactor.com, where they can buy all these products over the counter, because they’re just natural supplements. And so, that’s where they can go, NTfactor.com to find these lipids replacement therapy products, and find out more about it. And they can go to our website, the Institute for Molecular Medicine, which is www.immed.org. It’s like a media .org, and they can see the scientific results and the clinical trials.

[Damien Blenkinsopp]: Great, thank you so much. We’re going to put all of this in the show notes so people have all the references to everything we’ve spoken about today. Would you recommend they take the straight version of NT Factor? Because there’s these different combinations of things.

[Garth Nicolson]: Well it depends on what people want to do, and it also depends in a lot of cases on what people could afford if they’re buying supplements and stuff. The minimum thing they need is the NT Factor lipids.

Now, the more complex formulations like the one you’re taking cost more because they have a lot of other ingredients that are very costly. But if they want the initial punch, they need to take at a minimum the NT Factor lipids.

[Damien Blenkinsopp]: I see, that sounds like the big lever.

So Garth, thank you so much for your time today. Just on a personal note, are there any data metrics that you track for yourself? Either on a routine basis or a once yearly basis for your health, longevity, or performance?

[Garth Nicolson]: Well of course we look routinely at membrane lipids, for example, in our blood. We look at things like homocysteine and so on – and my levels are very low. I find that I feel better on NT Factor and, by the way, I have gone on a trip recently and I forgot to take it along, and I suffered because of it.

[Damien Blenkinsopp]: Oh no.

[Garth Nicolson ]: I feel very strongly about taking it on a daily basis. So I’ve seen it in myself. I mean I know that I can recover much faster from travel associated problems, for example, from illnesses and so on and so forth if I take the NT Factor.

And that’s what other people reported back to us as well, it’s not just my own personal results. We get a lot of feedback from a lot of people who are taking this, and now tens of millions of doses have been given to patients and subjects and so on, in various forms, and so far we haven’t had any complaints. And that’s a good news.

[Damien Blenkinsopp]: Its great news, it’s amazing news. Thank you very much for your time today, Garth. Its been great to have you on the show.

[Garth Nicolson]: Sure. Thanks for having me.

[Damien Blenkinsopp]: Aubrey, thank you very much for coming on the show.

[Aubrey de Grey]: My pleasure, thank you for having me.

[Damien Blenkinsopp]: So, aging is a disease. Obviously this isn’t what everyone thinks today, so why would you describe aging as a disease?

[Aubrey de Grey]: Well, it is actually because that is a controversial use of terminology I don’t tend to do that. I tend to try to sidestep the ambiguity of the terminology, first of all, and cut to the chase. So let’s say whether or not we choose to call aging a disease, what we can certainly say is that it is a medical problem. It is bad for you. It makes your body and your head work less well, and eventually it kills you. And that is what I call a medical problem.

[Damien Blenkinsopp]: Okay, fine. When you are looking at it from this perspective, are there things in previous interviews where I have seen. When we are young we can die and we can get injured from certain things. And when we age, when we are older in our 40s and 50s, we tend to get other health conditions which you could say are linked to aging. Are there certain conditions where you could say that if we didn’t age, we wouldn’t have to put up with these health or functionality restrictions?

[Aubrey de Grey]: Actually, yeah. And actually let me elaborate on that by referencing your first question about the age. I think the big problem with telemetry, with the use of the word ‘disease’ is not so much that we don’t call aging a disease. The problem is that we do call things like Alzheimer’s disease and cancer and atherosclerosis – we call them diseases. That is the mistake and the reason it is the mistake is because actually the difference between those things and the things that we rightly call diseases like infections is a much bigger difference, both in terms of the symptoms and the progression of the symptoms and the ways that we might be able to treat them. That is a much bigger difference than the difference between both of these, on the one hand. And the aspect with aging that we don’t call a disease – like declining function of the immune system or a loss of muscle or gaining of fat or whatever.

I think that if we are looking truly accurate and instructive, useful classification, if you like, of the various ways in which we can get sick then a much better one is to say that aging conflicts with everything that goes wrong with the body or the mind, predominantly for those people who were born a long time ago. And diseases are things that can affect young people just as much as older people.

[Damien Blenkinsopp]: Right, so the distinction – just to give some examples to the audience, would it be things like Alzheimer’s, Parkinson’s, even multiple sclerosis? I don’t think people tend to get that before the age of 30, for instance. Cardiovascular disease – would all of these kind of things be linked into that area?

[Aubrey de Grey]: Kind of, yeah. Certainly multiple sclerosis a bit of a gray area, whether you would really call it an aspect of aging – not just because it happens rather earlier than the other diseases you listed, but also because it certainly doesn’t happen to everybody. Whereas the diseases of old age, the commonest ones – whether it is cardiovascular disease, cancers, Alzheimer’s, these things tend to affect everybody at more or less the same age. Of course, some people die of one thing and some people die of another thing, but the only real reason for that is because of small differences in the rates at which different people accumulate the damage that results in these diseases. But most people who die of cancer die with Alzheimer’s in some level or other. Most people who die of atherosclerosis die with cancer. It is just that it hasn’t got so far along.

[Damien Blenkinsopp]: Right, so in your book The End of Aging, you describe the seven causes of aging. Would all of these be classified – would it be correct to call them some type of damage to the body?

[Aubrey de Grey]: I would call them damage, yes. In fact this is another kind of terminology question. I would say really that the best way to define the use of the word damage, in relation to aging, is that we would say that damage consists of exactly those changes to the structure and composition of the body at the molecular and cellular level that on the one hand arise as side effects of being alive in the first place, side effects of the stuff that the body does to keep us alive from one day to the next. On the other hand, they accumulate throughout life. They get progressively more and more abundant and eventually they get more abundant than the amount that the body is set up to tolerate, so that means they start to impair and eventually completely eliminate their physiological function.

[Damien Blenkinsopp]: Right, so there are clearly changes which take place because of aging, because of the processes that are going on as we are living.

[Aubrey de Grey]: I would say that they are aging, it is not so much by aging or they think they are aging, but the nature of aging is the changes in molecular and cellular structure.

[Damien Blenkinsopp]: Right. That is a nice way to put it because most of us think of aging as what we are looking at outside the body – the wrinkles and when you are looking at people you can see that aging. but in a respect we could say that the actual things you have defined and are changing within the body would be aging. so could you please outline what those are and which ones are the most important for you or if they are all the same? What is this kind of framework that you have and which ones are you most focused on currently?

[Aubrey de Grey]: The classification – there are seven major categories. It was really the big breakthrough that allowed me to see that the repair of damage was not only the most promising approach to combating aging with medicine, it was actually a feasible approach that could realistically be implemented within a matter of decades. If you have got 1,000 different things to deal with, then 1,000 different therapies are going to take a long time to develop. Well, if you can classify them into a much more manageable number of categories, such that within each category you are basically doing the same treatment for every example within the category and then the whole thing becomes much more feasible-looking, and that is exactly what I was able to do. So the categories are very simple things like having progressively-fewer cells in a particular organ or tissue because cells are dying and not being automatically replaced by the division of other cell. Or we accumulate molecular waste products in the cell because the cell is creating this waste product as a byproduct of something it needs to do. And the cell does not have any machinery either to break it down or to excrete it, so it accumulates.

Now, in each of these things we can look at and we can point to particular diseases and disabilities of old age that are predominantly caused by one or another of these things, so that is what we work on. And yes, we feel that all seven of these categories of damage are equally important. Certainly – well, there is one exception I guess, which is mitochondrial mutations where we can’t 100% certainly say it matters as much as the others. Actually, it might matter more than many of the others, we don’t know. But all the others we can say they matter pretty much equally as much because we can go into a particular nature, age, relation, or [pathology 00:11:42] and kill people at more or less the same age driven by that damage.

[Damien Blenkinsopp]: I see, so you are saying that pathology can be linked to each of these aging processes?

[Aubrey de Grey]: Yes, for example, molecular garbage inside the cell I just mentioned, that is definitely the reason we get heart disease, atherosclerosis – molecular garbage outside the cell is a major cause of heart disease in certain areas. Cell loss is the major cause of Parkinson’s disease, and so on.

[Damien Blenkinsopp]: Great. Thanks for that clarification. So you have outlined a roadmap to basically end aging and you have brought to light two concepts that I understand there are like bridges and there is something called longevity escape philosophy. Did you explain how these are eventually going to end aging or stop us from having to go through this process of aging?

[Aubrey de Grey]: Sure. So first of all, let me talk about bridges. That is actually not my terminology – that comes mainly from [Ray Kurzweil 00:12:40] who has often pointed out that there is a certain amount that we can do today to postpone the ill health of old age, and that is good. That is all very well. But there is actually more. Maybe we will be able, some of us anyway, to postpone the ill health of old age today with methods already available well enough to still be around in time for therapies that are not yet developed, because they haven’t yet been developed. If that can be done then of course we get an additional amount of life and we may be around for the next generation therapy, and so on.

And that concept – well, he normally talked about three major failures – what we can do today, what we might be able to do in the next couple of decades with our technology, and then what we might be able to do in decades after that using more of the non-biological solutions such as nanotechnology. And that is a fine way of putting it. Certainly the biotechnological approaches that he favored are pretty much identical to the ones I favor. And nanotechnology is certainly not an area in which I can claim much expertise, but I think he is more or less on the mark there, as well.

There are some where we part, actually, Ray and myself, as to how beneficial for most people what things are today, things that you can do already. And I think that [Bridge 1 00:12:40] as he calls it may not be much of a bridge, but by large the concept – we stand together on this concept. So the longevity escape philosophy, which you mentioned, is indeed from a phrase that I invented. And here I am not splitting the process of getting from here to indefinite longevity into that particular number of phases, like three – I am just saying that once we get a certain way along this process we are safe because we will be improving the quality and comprehensiveness of these therapies fast enough to stay one step ahead of the problem, essentially be repairing the damage that we couldn’t yet repair well enough that the overall abundance of damage will at no point reach a level that exceeds what the bod is set up to tolerate.

[Damien Blenkinsopp]: Right, and this relies on the concept that medical technology and biotechnology will be advancing exponentially?

[Aubrey de Grey]: Oh not at all and this is something which – and again I talk a lot with respect to I owe to information technology that we can see there is an accelerating track where progress is made at a faster rate as time goes on. In the case of longevity escape philosophy that may well happen, but the key point is it does not need to happen. In fact, if we are able to say 20 years from now or 30 years from now to reach this point where people are eventually not getting older, they are getting repaired as fast as they are aging, then it turns out that thereafter we can actually proceed at only that same pace and perhaps even slow down a little bit and will still be doing well enough simply because the rate at which the damage we cannot yet repair is accumulating will diminish as the types of damage that we can’t yet repair become fewer and fewer.

[Damien Blenkinsopp]: Great. Thank you for those clarifications. So what, for you, is the first and most important step? Right now are you really focusing – because you do funding of research and you kind of prioritize things – are you kind of prioritizing any of these steps in particular? Are you are trying to spread your investments so that you kind of manage the risk?

[Aubrey de Grey]: Very much the last, we are spreading. We have our fingers in all of these fires because we feel it is pretty stupid if we focused on some of them and then the other ones didn’t get done by us or by anybody else and people carry on dying on schedule even though most of the problems have been fixed. So we need to make sure, especially for the areas which are least fashionable, are being most severely neglected by other people, that it is vital for us to move forward. In fact, that is the only criteria that we use that really does determine what we choose to work on and not to work on. So the real manifestation of it is that we do very little work in stem cells. Stem cell work is very limited simply because so many other people are already working in that area. It is very burgeoning, very fashionable. So our work effort would be a bit of a drop in the ocean where we are the leading group working in many of the other areas.

[Damien Blenkinsopp]: Great, so basically you are choosing the least fashionable topics so that other things get pushed on it? And we actually do need to fix all of these problems. I mean, that is your assumption – in order to extend life and create longevity?

[Aubrey de Grey]: That’s right. I don’t think it is even an assumption, I think we know it.

[Damien Blenkinsopp]: Okay, great, great. So one of your other books looks specifically at mitochondrial mutations and the free radical theory of disease. Why did you specifically write a book about that topic?

[Aubrey de Grey]: Great question. So that was a long time ago. That book was published in 1999 and it is actually the only other book I have written. I have only written two books total. It was simply the first area that I got interested in when I decided I wanted to work on aging, whether it being to do something about it. Of course, I started out knowing nothing about that subject. In fact, I didn’t know all that much biology. I had been a computer scientist for my research career until that point. So I had a lot to learn. And obviously you learn some things before other things just by random chance. I ended up gravitating into the area of mitochondrial mutations as my main focus before I got interested in the other things.

So for the first few years of my career in gerontology in the late 90s, that was what I was working on and that was where I published my first half dozen papers or so. And my very first paper came to the attention of a publisher who did low print run academic books and said – anyway, what I wrote, so he said that he liked what I did and asked if I could go on writing a book, so I said all right, and that was the result. So the material in there covers pretty much my first three or four years or gerontology research. And it actually was also the [inaudible 00:19:08] idea was cemented to the University of Cambridge and I got the PHD for it.

[Damien Blenkinsopp]: Great. So would everything you wrote in there still be valid today or are there things you have discovered which you would change, some of that?

[Aubrey de Grey]: So the fantastic thing is that more or less everything is actually still true. There have been, of course, some minor discoveries that have changed things, but the broad sway of what I was writing there is certainly still true with one big exception. That big exception is exactly the exception that you like to have – namely, as time has gone on, new techniques, new ideas, and new discoveries have been made that essentially provide shortcuts – they have made the job of fixing this problem easier. And that is true also for the book that I wrote for ending aging, which is not nearly half as long ago as I wrote the mitochondrial and free radical theory book. So, they are pretty good, the lead idea of standing the test of time so well – the seven point plan that we work on is pretty much identical to what I was describing more than ten years ago or 12 years ago. So that is really circumstantial, but nevertheless quite strong evidence that we are on the right line, that there is more to this robustly standing the test of time.

[Damien Blenkinsopp]: Well congratulations because that is not an easy feat given how everything is changing so fast in biology and so on. So you have talked a bit about – one thing you mentioned earlier was except for when you are talking about the seven different areas and causes of aging, you said that mitochondrial damage may or may not be one of the most important ones. Why is there that area of uncertainty around mitochondria specifically?

[Aubrey de Grey]: Simply because there is no one major pathology we can point to where we can say clearly that there is a chain of events from this particular type of damage to that particular pathology. In the case of every other – the other six types of damage, we can point to a particular pathology and say that it is established. It is not even a hypothesis, it is actually known and absolutely agreed that the main driver of that pathology is a lifelong accumulation of that particular type of damage.

[Damien Blenkinsopp]: Great. So is that because we need to do more research to understand properly this mechanism in mitochondrial damage so we can say that we understand it less than the others?

[Aubrey de Grey]: I don’t think so, actually. I think the reason is the actual fact of the biology, rather than our understanding of the biology. I think it is possible that mitochondrial mutations simply don’t matter very much in aging, but it is more likely that they do matter but only by a very indirect route. And if it is indirect then it may be very placebic and it is something that affects pretty much all aspects of aging but in a subtle manner. So if you look at my book in 1999, you will see that there is some discussion of a rather elaborate mechanism – in fact, it is so elaborate that a lot of people just didn’t like it because it was too elaborate, which basically says that if mitochondrial mutations are accumulating even to relatively low levels, they may be able to be disproportionately toxic by essentially damaging molecules in the blood stream. And if they do that then those molecules can get into other cells and spread the damage around and kind of amplify it. This model is still very much a hypothesis and it has by no means been shown to be true, but it hasn’t been shown to be false either. And in fact bits of it, occasionally here and there, end up acquiring little bits of supporting data. There was a paper actually put out in [inaudible 00:22:54] just a few weeks ago, which was the first one to support one little technical detail of that hypothesis which previously had been completely controversial.

[Damien Blenkinsopp]: Great, great. It seems to me that mitochondria have become quite fashionable lately, just from my perspective. I don’t know if you would agree with that, when you are talking about the least fashionable versus the quite fashionable. There are a lot of supplements that tend to target more mitochondria and the word just tends to come up a lot more.

[Aubrey de Grey]: So yes, in a general sense mitochondria are very fashionable. Lots of people work on them. They have the major pre-eminent conferences on mitochondria that are bigger than ever, and so on. But the particular question of how we might be able to restore health to cells that have been taken over by mitochondrial mutation, that is obviously a very, very narrow area within mitochondriology and that is not fashionable at all. We don’t know, but we think it’s because people think it can’t be done. It’s a nature of science that people work on, things that they think they can succeed on and get published and promote and those things. And that means the hardest things often don’t get worked on at all.

[Damien Blenkinsopp]: Right, absolutely. So like Dr. Thomas Seyfried is well-known for his ideas around mitochondrial and metabolism and cancer. Do your ideas connect with his or are they different?

[Aubrey de Grey]: I don’t actually know that name. Tell me about this guy and his ideas.

[Damien Blenkinsopp]: With the metabolic theory of cancer?

[Aubrey de Grey]: Okay, there are various metabolic theories of cancer, but go on – tell me the ideas a little bit and I will tell you what I think of them.

[Damien Blenkinsopp]: Well, the idea is basically about free radical damage of the MT DNA and once that is damaged the mitochondria are not functioning so they are not giving sufficient energy to the cells. The idea is that from there the cells start behaving in a different manner, which includes cancer.

[Aubrey de Grey]: All right, so certainly stated that simplistically that theory is not correct. Variations of it –

[Damien Blenkinsopp]: I am sure I am not doing it justice at all.

[Aubrey de Grey]: Variations on that idea may have some validity. Certainly we see in aging that normal cells that are not cancerous at all accumulate mitochondrial mutations. Only a small minority of cells do that, but the ones that do get completely taken over by that mutation. In cancer we don’t see those same mutations. We do see some mutations sometimes and certainly one thing that we see much more ubiquitously is a depression of mitochondrial function even in the absence of any actual mutations. So the [inaudible 00:25:36] and we certainly have a number of theories out there that describe how cancer cells may obtain some kind of advantage then and protect themselves from the immune system, for example, by doing things like that or reducing their oxidative metabolism. So if that is the general theory that is being put forward, then yes, there is a certain amount of validity to it. But the thing that counts is that there are an awful lot of ways this can occur. There are an awful lot of ways that cancer health can discover to escape the normal controls that stop cells from dividing when they shouldn’t. So they have to do a bunch of things like breaking down the intracellular matrix, they have to ignore the signals that tell them not to divide, they have to ignore signals that tell them to die. They have to, as I say, resist the attack from the immune system. All of these things are really hard and any cancer that has reached a size where it has come to the notice of the clinician it has already jumped through a million hoops. So there are a lot of different ways to be that way.

[Damien Blenkinsopp]: Great, thank you. So today we have a lot of things in the press – there are a lot of products and there is a fair amount of research around topics which supposedly could help to give us longevity. Some of these are caloric restriction and linked to that fasting, autophagy, mitophagy and then we have the telomeres, telomerase and some others. For any of these things that are available today, and we can stop and look at them separately, I understand that you feel that none of them are actually targeting any of the seven areas, or any of the seven causes of disease sufficiently to actually extend our life. So could you talk a little bit about why you feel that is? Perhaps you want to tackle the biggest one, which is caloric restriction, for example?

[Aubrey de Grey]: Yes, by and large the simple approaches that we have today are not even hypothesized to actually repair damage the way that science is trying to do. So the best that could be said about these things, the proponents will say, is that they may slow down the subsequent accumulation of more damage. So that is still good. That means you are postponing the age at which the damage reaches an abundance that is insupportable, but of course the later you start the older you are when you start doing it. And then even if it works, the less benefit you are going to get because you have already accumulated all the damage at the original rates. So that is bad enough, but yeah. So you can say I am also very pessimistic about the ability of the approaches even to slow down the accumulation of damage by a meaningful amount. In very short-lived species calorie restriction is very effective. We can certainly increase the lifespan of a mouse from let’s say two-and-a-half years to three-and-a-half years using calorie restrictions, and that is pretty impressive. But if we go further down the evolutionary chain and we ask about small invertebrates like worms, for example, that normally live only a few weeks, it turns out that calorie restriction can do a great deal more. You can multiply the longevity of a worm by a factor of maybe three or four by calorie restriction.

The unfortunate thing is that this correlation, this inverse correlation between the natural span of the species and the extent to which that lifespan can be multiplied by calorie restriction works the other way as well. So 20 years ago people did a calorie restriction experiment on dogs and they only got a 10% increase in lifespan instead of the 40% that you might get in mice. And more recently we had a couple of experiments that on for more than 20 year looking at monkeys under calorie restriction. They finally reported and they got less than 10% – in fact, one of them was basically faster. So it is not looking too good. The worst of it is that this is what we should have expected because it actually was predicted by evolutionary theory – especially simply because long famines are not so frequent as short famines. We are unlikely to have the ability – to have evolved the ability – to respond to long famines in a manner that would increase our evolutionary fitness whereas short famines we experience frequently enough irrespective of how long the actual lifespan is that it makes sense to have that ability.

[Damien Blenkinsopp]: That’s great. And of course, currently the more fashionable topic around caloric restriction and fasting is intermittent fasting, which is typically anything between 18 and 24 hours for most people. Do you have a different view of that and the idea of this, which is activation of autophagy which can help to clear up some of the cellular garbage?

[Aubrey de Grey]: No, it is absolutely the same. The kinds of metabolic changes and expression changes that are induced are basically identical, and a good approximation – whether you have continuous calorie restriction or intermittent fasting or whether you use drugs that essentially trick the body into thinking it is on calorie restriction when it isn’t like [rapamycin 00:30:59] or whether you use genetic modifications in model organisms that trick the body in that way, by turning on the same pathway. It is no surprise. All of these things are turning on the same response, they are just turning it on in different ways. So of course you are going to get the same response.

[Damien Blenkinsopp]: Great, thank you very much. So the other big area – I guess you could tell me if you see this as the other big area because you do a lot of these interviews and you probably get the same kind of rejections. I think the other big area is telomeres and telomerase, which has become very fashionable now. And I understand that of course you think that isn’t an area that is going to help us?

[Aubrey de Grey]: Sure, so the telomere is a critical part of the cell and the organism and we definitely need to understand how it changes with aging and the extent to which those changes are good or bad. But we definitely cannot say at this point that the changes we see during aging are uniformly bad and therefore the thing to do would be to stop those changes from happening. The reason we can’t say that is because it seems that large animals, or large mammals and certainly humans, have made use of the telomere as a kind of way to get a tradeoff – get the best of both worlds between two important aspects of aging. One of them being the inability of the cell to – well, let me back up and say it a little differently.

One of them being the increasing inability of cells to divide and the other being the increasing tendency of cells to get into a state where they divide when we wish they didn’t. Most of our cells, let’s remember, do not divide – or if they do, they only divide fairly rarely, on demand. Like, for example, skin cells – the bottom layer of the skin that divide like crazy when you have a cut, to close the wound. It is only a small proportion of our cells, a few cell types, the stem cells of rapidly renewing tissues like blood which divide regularly. Those are the only cells that have a potential problem of telomere shortening.

Telomere shortening is something that happens when cells divide because of the nature of DNA replication and eventually when cells have divided enough they end up getting telomeres that are so short that bad things happen in the cell. I won’t take the time to go into what bad things, but the cell basically gets unhappy.

So cells that divide rapidly need to compensate for this and they have an enzyme called telomerase which does so. They certainly don’t need that capacity because they don’t divide often enough. They just don’t make the same amount of telomerase. Now, most people believe that the reason why they don’t make it is so that if they mutate, or become cancerous, then the cancer will not be able to grow large enough to kill us because that will require enough cell division that the telomeres will get short and bad things will happen to the cancer cells and the cancer will just wither away. So the question is if we want to do better than what evolution has done, how do we address this tradeoff?

One way might be to make most of our cells create more telomerase, more of this enzyme. That would allow cells in the blood, for example, to divide more than they currently do. And that would be interesting because it might make the blood continue to work better and the gut continue to work better, and so on, but it would run the risk of exacerbating cancer. The alternative is to go the exact opposite direction to bear down on to telomerase and make it less of it. That might be a really good way to suppress cancer but it might exacerbate the more degenerative aspects in that it makes our blood age faster, for example. We simply don’t know which of these factors is going to better because really it is not just which of those things you do, it is also how you cope with the side effects that you are creating. You are going to make one or other sides of the equation worse, you have got to find some secondary therapy to alleviate that and we of course don’t know yet.

So a number of people are working on the telomerase stimulation side of the equation, going to rescue the aging of dividing cells by giving more telomerase and then trying to find some other way to deal with any cancer problems that might arise. And we are going the other way and saying we are still with cancer by suppressing telomerase and left the other cells to deal with the cell division problems that might arise.

[Damien Blenkinsopp]: Right. And that seems to be because cancer is one of the most sure things which is actually going to kill us versus the other side of the equation, which you are saying is more of a functional impact rather than a kind of end of life kind of impact?

[Aubrey de Grey]: Well, I wouldn’t quite put it like that. I mean, there is still the big question of the extent to which telomere shortening really contributes to the pathologies of old age, so definitely telomeres get shorter in the blood in older people, but nobody has really been able to show they get so short they cause loss of function. So we actually may not need to worry about that in a currently normal lifetime But for sure, if we were to suppress telomerate in the manner that I have been talking as an anti cancer therapy, then we would create a problem even if the problem doesn’t already exist.

[Damien Blenkinsopp]: Right – when we are dealing with really complex problems it has been shown that can often be the case for therapies. So a key thing we talk about in this podcast is any aspects of quantification and with respect to longevity I am wondering if there is anything that you feel that is worth monitoring to track how we are aging? Now, currently it is fashionable with telomeres to measure the telomeres and they have indexes which say your telomeres versus someone else your age are above average or below average in terms of how many you have left, basically. Are there any biomarkers that you feel can validly track the progress of aging and perhaps how it varies between different people based on their lifestyles, their genetics, or any other factors that might be affecting the rate at which they age?

[Aubrey de Grey]: That is a really tough question. They don’t actually age, the Natural Institute of Health paid a huge amount of money several years ago, many years ago now, into a long-term study trying to identify biomarkers of aging that were really reliable and it was basically completely unsuccessful. They basically found nothing. Now, people haven’t given up on this but the reason they haven’t given up is the complexity. Essentially there are a couple other things you can die of, so how do you put aside whether one means by a biomarker of aging. Well, you have to define that some how, its another way of saying the predictor of how long you are going to live, what your remaining longevity is, or that you will remain in healthy longevity, but then you have to define health and it gets a little bit fuzzy as well. So it is actually quite hard to even define what you mean by biomarker of aging, but even once you have gotten past that difficulty, because there are so many different things that go wrong you don’t expect to have one simple or even fairly simple number that says something like this.

You expect, one would think, that as you get older you are as old as your weakest link. So you are going to expect that you would want to measure a lot of things and each of them points to a probability of getting a severe case of this or that type of age-related pathology in this or that amount of time. And certainly some things are more influential than others. These things affect each other and we may be able to point to things that are a bit more indicative overall of the probability of death or disease of all types in old age. But it is a very – it is not an exact science, put it like that. I have been lucky enough to have my biological age tested, which I have been able to do maybe four times now over the past decade or more. The test I have been able to get done on me involved measuring probably 150 different things in my blood as well as all manner of physiological and cognitive tests. There is no one number that comes out of that, really. There is no one useful number. The only thing that really usually comes out of it is what to pay most attention to, what seems to be changing more rapidly or seems to be problematic levels or that of other people of your own chronological age, those sorts of things.

[Damien Blenkinsopp]: Right, so there are 130 markers. Would many of those fit within your seven areas of damage and kind of be related to that?

[Aubrey de Grey]: Oh certainly. Certainly not now because the things that one measures in the blood aren’t metabolized. These are small molecules that are constantly being ingested into the body or synthesized by the body or destroyed by the body or excreted from the body. The blood stream is just this pipeline, right? It is just this network of roads that take things from one place to another and particularly it shortens molecules whereas the seven types of damage that I talk about, types of molecules or cells, the molecular or cellular changes that accumulate over time. So in other words, yes, the concentration of a particular small molecule in the blood may change but that is because of subtle changes in the set point, in the equilibrium between synthesis and destruction or ingestion and excretion of those molecules, which are kind of readouts of the level of damage elsewhere – maybe of the activity of enzymes or the activities or numbers of certain cells, for example. But they are not the damage itself, they are readouts of the damage.

[Damien Blenkinsopp]: Okay, great. So if we wanted to live longer today – I mean, I know one answer which we are going to definitely come up with at the end which we need to talk about, like helping you fund the different areas because you see that as the most important to targeting these areas that we are not really looking at – but for the people at home who are concerned about their longevity, what would be the best strategy for them in terms of thinking about their own health?

[Aubrey de Grey]: I wish I had a better answer to this, I really do. Certainly I know that there are some people – if you are an unlucky person, so Ray Kurzweil – come back to Ray Kurzweil again because of course he is well-known as someone who thinks that one can make a big difference to one’s longevity using supplements and so on. He probably is making a substantial difference to his own longevity that way, but that is because his own longevity by default was probably going to be rather shorter than average. He has a lot of cardiovascular disease in his family, he came down with type 2 diabetes in his 30s, which is pretty unusual even though it is not unheard of. And he has been able to really completely fix that using his regime that he developed himself and I totally applaud that. What I can’t do is say that this would apply to people who are already doing okay, especially those doing better than average, like me. Only if you are somehow unlucky, we have simple ways that may be able to somewhat normalize your rate of aging. Now, of course, on top of that, there is the fact that there are plenty of ways to substantially shorten your longevity by smoking or getting seriously overweight or eating a very poor diet, for example, but you didn’t need me to tell you that. I bet your mother told you.

So unfortunately over and above that, as things stand, we cannot point to anything that can appreciably help most people. And that of course is why I always say the only thing you can really do is buy more time – not by extending the time that you stay healthy but by reducing the time before therapy had come along that would actually do much more than anything that exists today.

[Damien Blenkinsopp]: Right. So I will kind of run by you the way I think about this and see if you have ideas on this, to see if this is a decent idea or not. The way I talk to my friends and stuff when they ask me these kinds of questions is I say that basically you want to manage your biggest risks, right? So if you were talking about Ray Kurzweil has cardiovascular risk in his family. For instance, you had a 23&Me or other set of genetic tests which point out that with some probability you have – for instance, I have a higher risk of lung cancer than most people and a couple of other things in my profile and people have different risks. So I suggest they look at that and then potentially they look for the biomarkers related to that on an ongoing basis rather than the genetic longer-term risk. And they monitor that and they also look into the things that can reduce that specific health risk and to reduce the risk and to limit the risk of them actually getting that biggest risk. So it is kind of plugging the biggest gaps they have of shortening their lifespan. I am just wondering if you think that is a reasonable approach?

[Aubrey de Grey]: For sure. I think in general for most people if you have got a risk factor that puts you at risk of being considerably shorter length than average, then you are going to know about it as a consequence of the kinds of metabolic tests I was talking about. But there can certainly be exceptions to that, things that truly don’t really affect your health as measured in normal ways, so that is all they do. Like suddenly some of them bite you in the backside. So that is the kind of thing that 23&me analysis might lower. But one also has got to be extremely careful in evaluating that kind of data because ultimately it arises from basic science. It arises from people studying particular genetic variations in the population and identifying correlations between those variants and the instance of this or that to these. And those studies are notoriously difficult to do and they have a notoriously low level of reproducibility because different populations are different and because sample sizes are limited, and so on and so forth.

[Damien Blenkinsopp]: Thank you. I always appreciate your answers because they provide a different context and perspective to everyone else so it is always very interesting to get that feedback. Let’s talk a little bit about SENS organization and what you’re up to there because this is your vision basically for making it happen. So you have different activities – and I also want to know a little bit about the [Methuselah Foundation 00:45:56] which you were formerly part of. And I understand that has some similar activities although it is going about it in a different way.

[Aubrey de Grey]: Sure, and let me actually start with the Methuselah Foundation because that makes more sense chronologically. The Methuselah Foundation is a charity, a 501-C3, that was created by myself and a businessman from Virginia named David Gobel in 2002, late 2002. Our goal was, of course, was to hasten the defeat of ageing but we didn’t have any money. So we started out creating a prize pot creating competitions in which we encouraged people to give up money that would go into a prize box and that the competition would be to beat the prevailing world record for mouse longevity. So with all you had to do the mouse that lived longer than any mouse had ever lived before. And of course we weren’t saying how things would be done and we set things up so that even a small improvement would be enough to win some proportion of the prize box. And it worked.

Basically our goal was to raise the profile of longevity research to get the word out and to get people more interested in the possibility of developing medicine to postpone ill health of old age. Well, we were bringing all this money in and right about 2005 or so we had enough money that we felt we could spend some of the prize pot in advance on actually pursuing specific research projects. So that is what we started to do and then things started going pretty well in that regard. But then we had a problem which we started to recognize in about 2008, which was that if you are a research organization you have got to obviously impress people with your competence and you have got your feet on the ground and everything like that and you are doing the right stuff. Well, if you are a PR organization, to get people motivated and so on, then you want to be the opposite – you want to be very popular, sensational, and glitzy. So we felt that it would actually serve the mission better if these two themes of our activities were between two different organizations, which would thereby be able to have very different styles, discourse, and styles of communication. So that is why we created the SENS Research Foundation, which was started in 2009.

SENS Research, of course, is also a charity – a 501-C3 so anyone can get tax back. And because this is going out internationally I should probably mention that we have a subsidiary in the UK which is able to take tax-deductible donations not only for UK citizens but also from most of mainland Europe. And if anyone wants to know about that they can contact us on the website and we will tell them more.

[Damien Blenkinsopp]: Thanks. We will put all the links in the show notes.

[Aubrey de Grey]: Excellent, thank you so much. So we created the SENS Research Foundation and it has been a truly, and the Methuselah Foundation and all the assets that have been given us research into the new foundation, so both foundations have been made in parallel since that time and I think we have both done pretty well and it is pretty good. So SENS Research Foundation, to go into a bit more detail – we are headquartered in Mountain View, California, just a little south of San Francisco. We have about 5,000 square feet of space in a facility, most of which is lab space. We have a variety of projects going on here. We actually have more than two-thirds of our research budget is not in our facility but rather in five university labs, again most in the USA, but some elsewhere. We have on outside Cambridge, Biotechnology Institute, and these projects are focused on all of the various areas of research there that SENS describes.

[Damien Blenkinsopp]: Yes, and I don’t think we have actually said what SENS stands for – Strategies for Engineered Negligible Senescence.

[Aubrey de Grey]: That’s right. We don’t often try to spell that out because it is a bit of a tongue twister. The name originally arose because of – well, basically historical reasons within gerontology. The phrase ‘negligible senescence’ already had a particular technical meaning and it seemed like a good place to start. But it is a bit of a tongue twister so we don’t bother to get people to remember that anymore.

[Damien Blenkinsopp]: Great, thanks. I will put links to all of those, of course, in the show notes. One last thing I just want to ask you, Aubrey, is from a personal stance you have said every few years you are going to test 130 markers or so of your own. Are there any specific things that you feel are important for you to personally track about your body for longevity, health, or performance?

[Aubrey de Grey]: Well, yeah. I mean, I think that first of all, coming back to something that we were talking about earlier, if any one marker is out of whack, you know, it seems like it is really telling a much more pessimistic story than the rest, then you have certainly got to try to ask yourself why, ask yourself whether it really is an outlier, whether it actually has that much impact given everything else as people say, things like that – but it is definitely not something that would be a good idea to ignore. So my one outlier the past couple of times I have done this kind of thing has been homocysteine, and I have no – I am not really sure why my homocysteine level is unusually high because everything else that it is supposed to interact with has not – but it is still something that I pay attention to.

From that, I can certainly say that there are certain things that are really at the nexus of metabolism, things that really if they are extremely good then you will be pretty safe, pretty much with whatever else is happening. Insulin is the best one. And of course, insulin is the hormone that mediates the absorption of sugar after you eat a sugar-rich meal so that the overall concentration of sugar in the bloodstream is maintained at as constant a level as possible. And the precursor of diabetes, type 2 diabetes, is something called insulin resistance, where the cells that take up sugar in response to insulin, which are mainly muscle cells, start to be a little sluggish about it and to only respond when they are given a large amount of insulin. So if your insulin is high, then even if your glucose tolerance, as it’s called, your ability to normalize your glucose in the blood is still good, then the indication is that it won’t be good for very long. Whereas glucose tolerance is good and also your insulin is really low then that says that you are in the best possible state. I would say if you have one thing, that would be it.

Perhaps another one would be triglycerides, whether it is a type of fat which seems to be good to have very little of in your blood stream and again, I am pleased to say that I do.

[Damien Blenkinsopp]: Thank you very much because those are basically the biggest diseases that we have today, like metabolic syndrome, so those are good markers for that. I guess one of the confusions with biomarkers we are always facing is that we are not sure if it is the end point. So one last question I did have for you was on a Palo Alto longevity prize. I am not sure if you know about that?

[Aubrey de Grey]: I certainly do and I am invited to it.

[Damien Blenkinsopp]: Oh, great. Because I understand they are running a competition or they have been running a competition for heart rate variability in connection with longevity.

[Aubrey de Grey]: That’s right, yes. So, businessman in the Bay Area in Joon Yun has put up a million dollars as a prize fund for progress against aging. It is divided, actually, into two separate prizes. One of them is looking specifically at heart rate variability, as you say, but the other one is a bit more general. It is looking at what they call homeostatic control or something like that. I forget the exact terminology. But the point here is that the competition is for the attempt to actually extend longevity [inaudible 00:54:06] in this manner. And I think this is great. I mean, the heart rate variability aspect is a bit unusual for people who have not really bought into the idea that this could be a real fulcrum of aging but it might be. And we think it is great to encourage research in any area that hasn’t been terribly well looked at. The main thing is simply putting a million dollars on the table as a great way to get people pretty excited, and a lot of people are paying attention now, especially since in the Bay Area there is a lot of identity of people interested in longevity in general. It’s a great way for a research foundation to be located. So yes, I absolutely applaud them for doing this.

[Damien Blenkinsopp]: Great to hear you are part of that also because we had heard of that from one of our previous guests. Aubrey, thank you so much for your time today. I love to hear all your different ideas of course because you are working at a very high level compared to most people, so you have this perspective that stands back a bit, which can be very helpful to people. Thank you so much for your time and have a great day.

[Aubrey de Grey]: Thank you, and to you. Bye.