Fasting, Aging & Longevity

Fasting, Aging & Longevity

A summary of Dr. David Sinclair’s Research by Thomas Delauer

Video Transcription

Introduction: Longevity is difficult to talk about and it’s difficult to research. What people think of as longevity isn’t necessarily what it really is. Longevity isn’t necessarily about how we live as long as we possibly can. It’s more about improving healthspan and delaying the onset of the uncomfortable things associated with getting older, like who doesn’t want to be 70, 80, 90 years old and feel good and play with their grandkids. It’s not about trying to live to be 193. It’s about trying to just live your best life possible. So keep that in mind when we’re talking about this research. I’m going to go through some of my favorite research from someone that I really appreciate in terms of content creation and research – and that is Dr. David Sinclair. Let’s break it down and we’ll discuss a little bit more on aging longevity.

In 2018, the World Health Organization classified aging as a disease. Now, what that means is we have to be careful with how we talk about aging. We have to talk about it as if we were talking about an actual disease. Really we want to just focus on feeling good quality of life, so this video is going to be a recap of some of my favorite pieces of research surrounding the world of longevity research from Dr. David Sinclair.

Dr. David Sinclair was recently on Joe Rogan, which kind of prompted me to do this video because he is one of my favorite researchers in this field. Hopefully this video could drive some traffic towards him, but also just get some attention to his research.

With the world of longevity, there’s really two pieces that you can look at. There’s sort of the genetic piece and then sort of the caloric restriction piece. Well, Dr. David Sinclair started out looking at genetics and yeast and he really found at that point, when he was finishing up his PhD or after he finished his PhD, he realized if they were activated by some particular gene called SIRT1, it activated sirtuins, yeast would live for a longer period of time. So he became very interested in that whole world of sirtuins and that’s something you’re going to hear a lot of in this video, we’re going to talk about sirtuins.

Essentially, they are pro-longevity genes – when we activate these sirtuins we increase their activity and we increase these pro-longevity effects within the body. Now, it’s kind of funny because in the beginning of Dr. David Sinclair’s research and the beginning of that whole time period, he was really under a lot of scrutiny because he looked at things a little bit differently.

He said he was looking at sort of external activators of sirtuins. One of the big things that he discovered was utilizing resveratrol, which is a powerful antioxidant to activate sirtuin. He’s kind of looking at it from sort of an additive form. Like what can we add in externally to activate these sirtuins that seem to encourage yeast and worms to live longer?

Whereas his PhD supervisor at the time was coming at it from a different angle and he was looking at caloric restriction as a better way to activate sirtuins via, what’s called NAD+, nicotinamide adenine dinucleotide. Just to put that into a nutshell, what that means is NAD+ is something that ultimately carries an electron to allow us to create energy.

The more NAD+ we have, the more NAD+ can carry energy, but also have some more leftover to activate sirtuins. NAD+ activates sirtuins and as we get older, we lose amounts of NAD+. Meaning we lose the potential to activate sirtuins, which definitely has a cascading effect on our potential aging. Right. Well, later on in like 2006, Dr. David Sinclair and his old PhD supervisor came together and wrote an article talking about NAD+ and how it can activate sirtuins. So the kind of like wrapped around and ended up going down similar paths anyway. That’s when all the research started with adding in supplements that can potentially boost NAD+ production.

NAD+ Boosters
Things like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), that’s when all that research started and people started getting really excited about that. Based upon this research from Dr. David Sinclair, we can potentially take these kinds of supplements and maybe increase NAD+ production and ultimately activate sirtuins and maybe get more of this healthspan benefit.

NMN & Resveratrol
Now, before I go any further, I’m going to lay out a full disclaimer here, I am not a doctor. I look at the research, I study the research and I give my opinion on certain things. I am a fan of taking NMN. I feel better with NMN. That doesn’t mean I do not like NR. Okay, but I do like nicotinamide mononucleotide. We’ll talk a little bit more about it. People are always very interested in the things that I take in that category, so this video is sponsored by a brand called Verso. They want to be very clear on that. Doesn’t mean that the content in this video is invalid because there’s a sponsorship on this video, but it’s because that’s the one that I generally take. So I did put a link down below if you want to check them out, it’s called Verso. And it is an NMN supplement that is also bound with what’s called trans-resveratrol, so kind of coupling the research from Dr. David Sinclair when he talks about resveratrol, but also the benefits of NMN.

So Verso is not affiliated with Dr. David Sinclair Verso, but it is the one that I use and hence why I’m recommending it. They store their product cold, like it should be, and then they expedite it to you, so it’s not exposed to a high temperature cause it really shouldn’t be exposed to a high temperature. So they are just my favorite one! I feel like they have top-notch quality. They have their dosing accurate and I feel like they just do a really good job and their an ethical company. Plus I just liked them as people because they’re good people.That link is down below if you want to try out using NMN now let’s get into some of my favorite research from Dr. David Sinclair.

Cellular Aging
Dr. David Sinclair published a study in the journal Cell, and this one was on stem cells and I find stem cells fascinating because as we get older, if we have declining stem cells, it can make cells basically irreplicable, like cells should be able to replicate, right? As we get older, if they have less ability to replicate, we have less ability to recover and yeah, that could be an issue.

What was this study that was published in the journal Cell by Sinclair? Well, in this case, Dr. David Sinclair found that nicotinamide riboside can actually restore some of the function of what are called muscle satellite cells. So satellite cells are cells that are just outside of the sarcoplasmic reticulum, just outside of the regular muscle cell and when activated, they sort of fuse and allow the muscle to grow. So without muscle satellite cells being activated, or without lower levels of muscle satellite cells, we really have an inability to build muscle. So in this study, which was conducted on mice, he found that healthy, but aging mice supplemented with nicotinamide riboside ended up improving their endurance by activating satellite cells.

So once the satellite cells were activated, they were able to allow the muscle to basically grow and fuse properly. This is just very interesting because I’m always interested in performance stuff. I’m also interested in aging and when it kind of intertwines like that, I find it fascinating. So that’s with nicotinamide riboside, but let’s take a look at some of this other stuff that he’s researched.

Vascular Aging
Vascular health is a huge piece. As we get older, we want this dense network of capillaries. Okay. This is going to improve what’s called tissue perfusion. Okay. That’s blood and nutrients and glucose and fats getting into the nooks and crannies of your tissue. Okay. If you have less capillary density, that’s less tissue perfusion, less nutrients being able to get to where they’re supposed to go.

Right? Well, Dr. David Sinclair published another study that was also in the journal Cell. Well, this study indicated that NAD+ and sirtuins were required for vascular endothelial growth factor. Now, what that is is that that is a growth factor that signals the cascade for angiogenesis, for us to grow new vessels and new capillaries.

So the details of the study were pretty interesting. So with this study in mice, they showed that an age related decline in angiogenesis was somewhat reversible with the addition of nicotinamide mononucleotide, with NMN. Well, it’s kind of funny because here’s what they did: They took mice that had a SIRT1 knockout. What that means is they took the SIRT1 out of the equation. Basically they eliminated it in those mice and then they had them run. Okay. When they ran on a treadmill, they ran for 11 minutes. They got exhausted after 11 minutes. Okay.

Now the other group was a control. So the control group did not have sirtuins knocked out. They still had their sirtuins there. They ran for 25 minutes to exhaustion, but get this: those that had overexpressed sirtuins, where they actually expressed them more, well, those mice ran for 46 minutes. So there was a very strong correlation with endurance and sirtuins, and it has to do again, with that angiogenesis, with vascular endothelial growth factor, which is pretty fascinating stuff.

What’s even crazier is they took a look at old mice, mice that were about two thirds of the way through their overall lifespan. Okay. And they gave them NMN; they injected them with NMN. So the old mice that did not have the NMN ran for 15 minutes before they were exhausted. The mice that were given the NMN injection ran for 25 minutes.

It shows we do have an age-related decline in these sirtuins and that could potentially, at least in mice, be sort of reversed a little bit with some NMN. Again, has to do with angiogenesis, which is cool because we’re basically supplying more nutrients to a muscle. I find this personally very fascinating, and I find this research from Dr. David Sinclair, probably one of my favorite pieces.

Mitochondrial Aging
So here’s a cool one. If you like to fast. Okay. This is some research that Dr. David Sinclair did on the mitochondria, just mitochondrial health. And it has to do a lot with caloric restriction and fasting. And this one, it was focused more so on SIRT3, which is a sirtuin that’s not talked about as much in the mainstream.

So this study was published in the journal, Free Radical Biology and Medicine and it took a look at the activation of SIRT3 via fasting or caloric restriction. They found that fasted mice had this SIRT3 activated and it was activated because of the reactive oxygen species, the stress that is induced by fasting.

Now, what does this really have to do with aging? Well, when you have more activation of SIRT3, you have better transcription of mitochondrial DNA, meaning that you can essentially get the activation of this mitochondrial unfolding protein that allows mitochondria to just go through proper, I guess, biogenesis properly. So you’re essentially getting the activation of the master regulator of mitochondrial biogenesis, which is called PGC1A. I personally find this fascinating because I’m into fasting. There’s no real reference to NMN or NR or NAD+ here, but we do know that fasting in general increases your levels of NAD+ and improves your NAD/NADH ratio, which means you have more available NAD+ to activate sirtuins. So the reason that fasting activates generally like SIRT1 is because you have more NAD+ that is not being used to transport electrons from food and therefore more available to activate sirtuins. Okay. So it’s pretty fascinating. Now in this particular case, SIRT3 was activated by the reactive oxygen species and the stress of fasting. So you have the stress of fasting activating SIRT3, but you have the netter NAD/NADH ratio influencing the activation of SIRT1. So if you’re into fasting, you’re a biochemistry nerd, you know what I mean? If not, you might be a little bit lost, but let’s bring it back to something that’s really cool.

Metabolic Health
Talking about high fat, high sugar diets and metabolic health – this is another one of my favorites; they’re all my favorites, I love his work. This study was published in the journal Cells, also by, of course, Dr. David Sinclair. This took a look at mice that ate a high fat, high sugar diet, but were born from obese mothers.

Well, okay. What are we looking at? We’re trying to look at the influence of NMN and how it can help this or how we can just improve, and how NAD+ might be able to improve this overall. Well, the whole world of like maternal epigenetics, like when you have an obese mother and what passes on to a child, that’s a very heavily researched world. It’s pretty widely known that if an overweight or obese mother gives birth to children, that those children are going to run a higher risk of being obese because those epigenetics are very powerful. Well, what does this have to do with Dr. David Sinclair’s work? Well in this study, you found that with these mice, that impaired glucose tolerance, that was a result of just, again, high fat, high sugar diet, and being born from an obese mother was ultimately reversed or at least somewhat reversed by utilizing NMN for just eight days.

So that’s a pretty powerful thing. When you can change the epigenetic influence of a child in this case, a child mouse. Right? So basically this mouse was born from an obese mother. The mouse was probably prone to being overweight from a genetic standpoint. Plus it was eating a high fat, high sugar diet, but utilizing NMN improved its ability to deal with that and improve glucose tolerance. It also decreased the amount of hepatic fatty acid synthesis. So that means that it ran a lesser risk of developing a fatty liver and having that kind of synthesize so very interesting stuff. Again, this is all research that’s done in mice, and you can say whatever you want about it being applicable to humans. And I make sure that I offer that full disclaimer up there that anything with this is just research, right? You know, you could apply it to yourself. I am an experimental nerd and I’m totally down to experiment on stuff. If I look at the research and it seems conclusive and Dr. David Sinclair has done so much research, I feel like someone that I trust.

So I encourage you to check it out. I encourage you to look at his work. I encourage you to look at the podcasts that he did with Joe Rogan and give it a listen. And I also encourage you to experiment and test this out yourself. Try different things out.



VERSO® is not affiliated with David Sinclair, or any of his work. David Sinclair does not endorse any specific NMN or Resveratrol brands.


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