June 4, 2023

Learn how Dr. Nir Barzilai is revolutionizing life extension treatments using metformin in the first Phase 3 clincial trial to target aging.

We need to know about animal models that in this animal kingdom all animals are aging in similar way like humans it’s a conserve pathway animals that are aging have biology and if they have biology we probably can target this biology and see if it affects the rate of aging and we’ve done it in the lab we took warms and mice we took flies and rats and primates

And we treated them either by genetic manipulation or a interaction with the environment or drugs that some of them are even in human use and we are successful in extending not only lifespan but health span in those animals we did it again and again we have a body of clinical preclinical work that suggests that we we can do it let me give you this example there

Is a very interesting chemical that is called rapamycin and rapamycin is in use in people after a organ transplant it’s an immune modulator a rapamycin affects a nutrient sensing pathway that’s called mtor and the experiment that you see in the slide is experiment that was done in three different labs using the same drug in different concentrations and when you

Give rapamycin to mice you see in the blue line are the control that didn’t get the drug but with increasing doses of drug those animals live longer there are studies now to give rapamycin to dogs and see if it affects their aging there is even a study where they took elderly people and gave them rapamycin before immune immunizing them and showing that their

Immune response was better against the virus so that’s an example of a drug that’s out there unfortunately this drug is not yet safe for chronic use so it needs much more development so what can we do what can we do in the meantime how can we go from animal studies to human studies well some of you might have heard about a drug that’s called metformin so i have

Two pills of metformin that’s all a diabetic patients need in order to control their diabetes for a long while i hope you can see it now and people who take this drug if they are not diabetes it will prevent diabetes but and by the way when you give it to animals they live longer and they live healthier so we know that from the biology of aging but it’s a drug

That is safe has been sixty years in use is generic so it’s cheap and but it has curious side effects one of the side effects is that people with diabetes if they’re on metformin is compared to other drugs they have 30% less cardiovascular disease if they are on metformin they have 30% less cancer if they’re on metformin whether there are diabetics or not they

Have less cognitive decline and less alzheimer and this is the data that really got to me this is a study from the uk where they took 200,000 people half of them are controlled in the red and black line and watch their mortality now the blue line is for a drug called sulfonylureas the people with diabetes on tzuf illyria had higher mortality we know that people

Diabetes severe mortality but in the greenline are the people with metformin and the people who use metformin it’s not only that they lived they had less mortality than the people with diabetes who are treated with other drugs but they had less mortality than the control significantly less mortality than their control they had diabetes they were more sick to

Begin with and they were more obese to begin with and yet they survived later so that shows us that metformin can be really a great tool in order to target aging why am i saying that metformin is a tool well first of all we have to do the study and we have to do it right and with the help of the american federation of aging reefs research we launched this study

That’s called tame targeting aging with metformin and in this study we’re going to select elderly people and randomized them three thousand people we randomized them to placebo in control and what we’re going to look at is the onset of diseases which diseases we don’t care we’re agnostic to the disease every disease will get a point it’s all about aging so

We’re going to look at cardiovascular disease and diabetes and cancer and dementia and cognitive decline and death and everybody gets a point but we’re going to show how much forming changes this rate of aging and we’re going to have some other secondary outcomes to read the pic the functional decline of aging seen those slides on the hallmark of aging this is

The european one has nine pillars with brexit they’re losing to i here and and this is the american one that have seven but please concentrate on the american one and the network in between and i think this is very important i’ll give an example i wondered what examples you were going to give i’ll give an example that that you you haven’t heard yet annamaria

Cuervo at einstein is an expert on protists this or more correctly she’s an expert on auto feed you know tofu g is the garbage cleaning mechanism is in our cells it’s actually a green energy garbage disposal mechanism in annamaria cuervo with genetic methods and with drugs have been able to increase the clearance of garbage in our cells she prevented and cured

Parkinson in in models and alzheimer in models because the neurons are really accumulating this a better protein and they’re really freaking out from this dimension but the important point here is then when she does did she effects also the stem cells the metabolism and the inflammation and that’s common to a lot of the drugs that we’re testing there they’re

Supposedly we’re targeting one thing but because of the connectivity we are influencing other we still want to have enough tools for everyone but we can start making a lot of difference by starting even with one aspect of that and i would summarize what we’ve done and what you’ve heard before that healthy lifespan and and i want to say that it’s health healthy

Lifespan what we’re trying to achieve is health spent in my mind longevity you know with the commercial you know you’ll be healthier the side effect you’ll have longevity can you pay for it you know i think longevity is a side effect but we can target health spin and we’ve targeted health spin in many models we can do it in nematodes and in flies and in mice and

In rats and in in in monkeys and we can do it by interaction with the environment or with our genetic manipulation or drugs and really the most important thing that some of those drugs are actually in human use and i would say the following since our maximal life expectancy we think is about 115 right there’s somebody who live to be hundred and twenty-two but

It’s about 115 and since we die now before the age of 80 there’s 35 years potential without changing our body in any substantial way that we could realize now and a low allow george to move on on can we extend it below or can we make it better but there’s a way to move right now i also should mention that the niƱa had this intervention testing program and it’s

Just to show you some of those drugs that are given to animals and the control in three different centers and if the animals that are kind of shifting to the right are those who surviving longer and there are a few points to realize here a first of all that a lot of those drugs are extending lifespan on the bottom right the combination of rapamycin and metformin

Has the world record in longevity of 24 percent increase in health span and and in lifespan and much more that in health span also you notice by the rapamycin and there’s an error there on the bottom middle you can target aging later in life and still get in effect it’s not it’s never too late to target aging i bet the sin olympics that you heard about from the

Director is something that you target later in life because you need to have more senescence cells and maybe some other intervention actually like the one george mentioned you have to start a earlier in life and we’ll have to figure that that out but their example let’s figure out for a second why are we afraid of aging now woody allen says i’m not afraid of

Dying i just don’t want to be there when it happens but that’s not really what we’re afraid of we’re afraid of the diseases of aging we’re afraid of getting in disease and getting a treatment both the disease the treatment is not so effective against the disease but it has side effects and then we get another disease and another treatment and and very soon we are

Accumulating three and more diseases with many treatments that have side effects and also interaction between between them this is really failing what i want to show you in this figure is look at all those diseases that are age-related diseases and they come in different colors and i want to show you the relationship between death from those diseases in age and

Take the light blue line on top first this is the death from cardiovascular disease according to age the risk goes from a number 5 there to 5000 the risk of dying from cardiovascular the major risk for dying from cardiovascular disease is aging now people tells you hey there’s cholesterol but cholesterol is a three-fold risk aging is a thousandfold risk but this

Is not only for heart disease the next line there the red line is cancer okay and it’s parallel line so the major risk for cancer for any cancer is aging also and that makes you maybe understand that treating one disease of a time the most that you can expect is to exchange one disease for another you know if if you get a heart disease if you get a myocardial

Infarction or you you walk into the emergency room you get a stent or you get a bypass you know those people that are now safe from from local treatment to their heart in two three years a lot of them are getting diabetes and cancer and alzheimer’s because we never treated or thought of treating their aging just one disease that just one disease in the time and

That doesn’t it work so well so how do we move how do we move for from understanding this aging and this problem in trying to move on so back to my centenarians and there are three things i want to show you the first thing is in this graph which depicts really the how many of those centenarians in our control are disease-free in the beginning if you see the

Green line which is for the control everybody is pretty much a healthy and then at a certain age they’re starting to be sick and at age 80 most of them are sick very few people are not sick but if you look at the blue line that is for centenarians you see that it’s all delayed there they’re starting to get sick later and at a later age a lot of them don’t have

Diseases wow what a relief right we didn’t want to find out that they get disease like everybody else and then they live with the disease for all those years but they have twenty to thirty years that they don’t have diseases now you might say okay but but after all we’ll learn about the interaction between the environment and an aging so maybe they’re just doing

What the doctors are telling us to do now and the answer is no okay 50% of them are overweight or obese 50% of them are smoking less than 50 percent are doing even moderate exercise i’m talking about a walking and bicycling or or or or or work at home so this story is really not their interaction with the environment but in spite of that huh how otherwise would

You explain the talan lived to be hundred and ten when she’s smoking for 90 years so what did we discover in their genes well we discovered clusters of mutation that changed the function of some proteins some of the proteins for example are important to lipid metabolism so our centenarians have and their families have high levels of hdl cholesterol it’s the

Good cholesterol and this is associated with some of the mutations that they have some of our centenarians have mutations again cluster of functional mutations in their growth hormones which suggest actually that giving growth hormone to elderly which is practiced sometimes in the united states is really not safe but above all there are a biotech companies like

Khobar or pharmaceuticals like merck that have taken some of my data in are developing drugs but the drugs that are developing are targeting one disease and not only aging so how can we move to target aging so what are the challenges to translate our advance in understanding aging to humans so this is the challenge in every other disease you find the biology and

You have biotechs and pharmaceuticals and you develop drugs and the drugs are targeting the disease and you actually come back to the scientists and said you know we’re running out of pet and maybe there’s another mechanism when maybe we’ll do another drug and everybody is happy with those diseases for aging the fda doesn’t have an indication to target aging and

We feel we and when i say we we were a bunch of scientists that we feel this is the one that’s holding us most and why is it holding us because if if there is no indication the health care providers do not pay for their clients if they don’t get pay for their clients then the pharmaceuticals are not going to do those better drugs other drugs cause they have to

Have a business plan so for us the major obstacle has been the fda and we against bunch of scientists found a way to deal with it we took a drug by the name of metformin that extends health span and lifespan in animals we understand a lot of the biology of that metformin is the first line a for type 2 diabetes is generic very cheap drugs one of the cheapest drugs

Transcribed from video
Nir barzilai Compilation | Metformin | TAME By Increase Maximum Lifespan