CAN WE SLOW AGING EFFECTS IN HEALTHY WAY ?

Today we know about how to slow aging in healthy way. So lets start...

 one of the reason that we study aging is that aging is the biggest risk factor of all kinds of chronic diseases you know you can name it type-2 diabetes dementia for example you know Alzheimer diseases Parkinson diseases you know cancer for example so those heart diseases as well so those diseases they increase dramatically exponentially when people get older so right now our current healthcare system is that we don't do much of prevention so like we treat people when there are already sick when they're already you know have their memory loss and there's not much we can do especially you know for Alzheimer diseases we can there's no treatment to reverse that progression of the diseases.

so if we wanted what so the goal is that we wanted to slow down the biology of your age right so like you can you don't get those diseases early on and then suffer for a long time so we want to make generally make people healthier we wanted to do prevention we want to give some people some you know some molecules and some therapy you know when there's already still healthy you know when they can still remember everything, they can still get up and run what we really want to achieve at the end so for you know a lot of people think we want to extend human life span I mean this is probably one goal but this is not our primary mission.

our mission is that we don't want ultimately extent the human life but we want to extend the healthy time of human life. I got it, healthy life span, thank you. Exactly Going back to the question of research subjects: east and worms.  Why yeast? I gave a lot of public talks when I worked at the Buck and when I told people that I use yeast this small creature that people use to bake bread make wine and cheese I think they see me like I'm such a weirdo some crazy scientist.

why do we study yeast and worms to understand us so actually yeast I mean even though it's a single-cell organism we share a lot of proteins between and pathways between humans and yeast for example so human we need to eat food with sugar to generate energy right so East also need to do exactly the same thing and then the pathway that they use to convert sugar into energy to their body is similar between yeast and us so it's very reasonable to study yeast and until you understand something about our body and another thing is that yeast are very small and they divide very fast so we can get our results super fast.

 I mean of course we can study the aging of mice the average life span of mice is about three three years and then the average lifespan of a yeast is about two weeks so you know at the end you can get result much faster and then you can design your next experiment and you can also do high-throughput stuff you can grow trillions of them in this area in a small petri dish right we can do drug screening you can do genetic system biology screening so because when I joined the lab Brian Kennedy he was one of the pioneer in aging research in yeast especially.

Where nobody thought then nobody was even thinking about using yeast to study the biology of Aging and then he came up with the idea is that maybe we can just bring the whole yeast genome which consists of six thousand genes so he wanted to know every single gene how does that gene affect lifespan or health span of yeast. He ended up discovering sirtuin, a magic protein which affects life span in yeast also in all kinds of animal models including human you know we have sirtuins too have seven different kind of forms of sirtuin. By using yeast we can actually get results faster and study every single gene in their genome so I don't think using other organisms we can actually achieve that goal in a short amount of time and also yeah worms yeah worms are another small animals they are multicellular animals and then they are very small like one millimeter long. 

you have to look at them using a microscope otherwise you don't see them, very short lived as well, average life span is 20 days means that you know you can get your result much faster and the pioneer who studied worms you know the biology of aging worms her name is Cynthia Kenyon she was a professor,  now I think she's a director or vice president in Calico, subsidiary of Google,  so before her nobody think that actually we can manipulate one gene than we can regulate lifespan people are always thinking about aging is you just completely wear out there's nothing can you know reverse aging and change the lives back.

so she just basically muted one genes and then she found out those warms lived twice as long leave twice as long so they pay from like 21 days to 42 days so that was amazing.  and then we also found from worms about growth hormone, we have it too! Okay got it thank you, all right there is a race between many research teams globally to create a safe medicine which slows aging so can you summarize for us where we are in this race right now yeah so like I said like people started looking at biology of Aging in the 90s right like before that like a lot of people just a lot of scientists din't believe that you can just change one gene and then you know extend lifespan or regulate the health span.

 But right now I think we're getting much much closer to the true answer what is the target at the end that regulate calorie restriction, regulate the nutrition sensing pathway which is mTOR pathway and then we already have small molecules they can regulate mTOR pathway so such as rapamycin is one of them and then there's tons of studies about this molecule can slow down age-related pathology you know like Alzheimer disease type 2 diabetes cancer and so and so forth so you know and another molecule like metformin, studied by Nir Barzilai,  he is a director the aging research at Albert Einstein College of Medicine so he actually starts a clinical study using metformin on people so I think we're getting really close to the answer I think in the in the next near future you know five to ten years.

We will have a much clearer idea of how to use the small molecules in a safe and regulated way to prevent you know the prevent to slow down aging and also you know not just small molecule there's also other ways you know like the stem cell biology is another big hot area and also you know senescence cells you know like we as we age our body accumulate those senescence cells that they don't die but they secrete those bad signals favorite cells and cause neighbor hoods like the develop cancer there's you know Institutes and companies start to develop small molecules which cam eliminate senescent cells. I know that one of your first research papers was about the impact of ibuprofen on Aging which it's  a regular medicine which is used for treating colds.  can you share the main conclusions from this research? yes of course so yeah when I published that paper that was I think was 2014 the end of 2014 .

so I actually bring a lot of public attention because everybody takes every profit right so if ibuprofen have some you know benefit with you know for healthy life span then everybody would like that so this research was also done with using yeast and warms so what we found out is that if we if we give east and worm ibuprofen small dose like low dose and then actually we found that they extend life span also they have better the worms have better lifespan.  they're healthier and then what we found out is that even though ibuprofen in human you know is - we use ibuprofen to suppress inflammation right it's anti-inflammation drug but what we found at least in yeast, that ibuprofen was very important for yeast to uptake the nutrition one of the nutrition here is one amino acid called tryptophan alright so we need tryptophan as like important nutrition you know to develop to grow we found out if we give too much tryptophan.

it's actually not beneficial for life that extension so an ibuprofen actually kind of eliminate or not eliminates decrease the up take of tryptophan and we found out that is crucial for yeast have a longer life what we're thinking about maybe ibuprofen also have the same function in higher animal models but we still testing that one of the take-home message is that so there's a lot of existing drugs so such as you know ibuprofen and then metformin I was talking about so people are already using them for you know 50 60 years so they are safe there so you don't need to develop you know like new drugs there's already probably some molecules that already on the market and we're taking them but we're benefits people have been benefited from those molecules just don't know what the mechanism is know also that you're very passionate about calorie restriction as a way to slow down aging so can you share with us some evidence from research on this topic? yeah 

so if there's a one method that's worked for every single animal organism testing in the research of knowledge of aging that is calorie restriction so that means that if you only give the animals about 70 percent calories that they supposed to eat and an animal has that food intake every day they live longer and healthier one of the most famous study is actually the study was started in the 80s so they use monkeys they use monkeys it was about like 25 years old study and then they publish in early 2000 they found out that calories restricted monkeys  they live I'm not sure if they relatively live longer but they definitely live healthier so if you just compare the picture of non calorie restricted monkey means that they could eat whatever and then calorie restricted money the calorie restricted monkey look much healthier

 so they have they don't have hair loss you know they don't have wrinkles they just looked like perfectly like a young monkey even though those two groups have the same chronological age.  so one of the idea is that we wanted to to find out what governs the nutrition sensing path way what is the mechanism that caused them to live longer scientists already found that there is a major pathway it's called mTOR signaling pathway  so mTOR is nutritional sensing pathway you know like it's actually very critical in our developmental stages because mTOR can cause the cells start to divide would grow grow bigger or depreciating and we also find out if we can successfully inhibit mTOR pathway function then we can make those animals live longer without you know starving them or doing calorie restriction well there is definitely a lot study has been going on and i think that our goal is that we wanted to find a way that can mimic how the calorie restriction works there is also other alternative way so  for example there are you know fasting or time restricted eating so what that means is that you know there's like five two day fasting you know like you only eat very small amounts of calorie in five days and then it can be beneficial for longer time. so I've done that I think the second day was really hard because there's a transition time butt owards the end of the fasting day I feel actually I felt good so I follow one of the papers that is published by Valter Longo from USC, the University of Southern California he's a big advocate off a sting yeah 

so I think fasting is fairly safe because you only do that for like five days and for people if people wanted to do calorie restriction for long period of time that you have to be very careful to know that you get enough nutrition right from short amount of food the calorie restriction for healthy people or you know like you and me we can tolerate fasting for like five days and then the study shows that after the five days fasting you know our ketone bodies go up which is a good thing you know,  glucose blood pressure drops, all the good things happen. I think one of the great thing about fasting is that when they test fasting animals they found that their organ shrinked and then the shrinking will be reverse done.