In short
The episode argues that glycine (a simple amino acid, also used as a sweetener) may improve healthspan and potentially extend lifespan, possibly by mimicking methionine restriction. It also contrasts glycine with trimethylglycine/betaine.
Guests
Dr. David Sinclair (Harvard Medical School, genetics/aging research; longevity scientist; author/co-author of Lifespan) and co-host Matthew LaPlante.
Guest backgrounds
Sinclair did his PhD on glycine metabolism in yeast (University of New South Wales/ Ian Dawes lab era mentioned) and later became a long-time sirtuin/longevity researcher; he says he consumes glycine daily and studies aging pathways.
Key claims
Glycine may boost collagen synthesis, increase glutathione via glycine plus cysteine (often via GlyNAC), reduce oxidative stress/inflammation/insulin resistance, improve memory and stroke recovery, and associate with ~11% reduced heart attack risk. Proposed mechanism: high glycine increases methylated glycine (sarcosine) excretion, consuming methionine and downregulating mTOR.
Notable examples
Human trial (glycine + NAC, ~7 g/day for 16 weeks) reported improved glutathione-related markers, oxidative stress, mitochondrial impairment, inflammation, insulin resistance, strength, waist circumference, and blood pressure; animal lifespan effects include worms (10–20%), flies (~10% males/~20% overall via GNMT upregulation), mice (4–6% in ITP; ~23–24% in Baylor study), and rats (up to 28% mean/31% max lifespan). Betaine is discussed as potentially beneficial for exercise/skin but likely opposite to glycine’s methionine-depletion effect.
Written by AI. May contain mistakes. Listen to the episode to check what was said.
Chapters
Tap a time to open that second in VOIntroduction to Glycine and Its Benefits
0:00 to 0:35
Learn about glycine, its effects on collagen synthesis, and its role in aging.
“In fact, this molecule has been around since the dawn of time.”
Exploring Glycine's Potential
1:17 to 2:13
Discussion on glycine's benefits, personal experiences, and research background.
“Today, Matt and I explore a simple amino acid that helps build collagen, supports our antioxidant defenses, and has extended lifespan in some mouse experiments.”
Exploring Glycine's Potential
2:15 to 2:34
Discussion on glycine's benefits, personal experiences, and research background.
“You'll get the gorgeous 100-page magazine, early access to Lifespan episodes, my longevity newsletter, clinical trial updates, AMAs, exclusive interviews, and a lot more to come.”
Exploring Glycine's Potential
2:41 to 2:51
Discussion on glycine's benefits, personal experiences, and research background.
“to the magazine, bonus material, and some personal gifts from me.”
The Importance of Glycine in Aging
2:57 to 5:04
Hosts discuss glycine's significance in human biology and its connection to aging.
“Well, today we have a really interesting topic we're going to cover.”
Key Longevity Pathways Explained
5:08 to 7:07
Introduction to the three longevity pathways: Sirtuin activators, mTOR inhibitors, and AMPK activators.
“And one of the things that we can do is supplementation.”
Understanding Sirtuins and Their Role
7:08 to 8:00
Detailed explanation of sirtuins and their importance in cellular stability and aging.
“So sirtuins are silent information regulators, SIR in the name, and they regulate many different things.”
The mTOR Pathway and Its Impact
8:01 to 9:23
Discussion on the mTOR pathway, amino acids, and their relationship with longevity.
“These are called the branched chain amino acids.”
The Role of AMPK in Longevity
9:24 to 11:23
Exploration of AMPK's function and its significance for maintaining energy balance.
“If you're hungry, you don't have enough energy, AMPK levels go up.”
Mysteries of Glycine in Longevity
11:24 to 12:20
Hosts delve into the unique effects of glycine on the established longevity pathways.
“There's a lot of things that these pathways do.”
Show all 24 chapters
Historical Context of Glycine
12:21 to 15:46
A brief history of glycine and its discovery as an important amino acid.
“It downregulates AMPK, which is the opposite of what you'd expect.”
The Fascination with Glycine
15:51 to 18:10
Discover Dr. Sinclair's journey in genetics and his interest in glycine.
“Yeah, well, if anyone's wondering what it looks like, we have a drawing of it.”
Glycine's Role in Health Benefits
18:10 to 19:26
Explore the various health benefits and theories related to glycine.
“Sequencing in those days, by the way, was very different.”
Glycine and Collagen Production
19:26 to 21:44
Learn how glycine impacts collagen synthesis and skin health.
“There are three ways that you've said this might be happening.”
Mimicking Methionine Restriction
21:44 to 24:22
Understand how glycine can mimic methionine restriction effects.
“And that's going to get us back to a place that we were at the beginning of this episode.”
Long-Term Benefits of Glycine Supplementation
24:22 to 27:34
Discuss the potential long-term benefits of glycine supplementation.
“And you've got to be careful about this, right?”
The Importance of Glycine Supplementation
28:00 to 29:38
Learn about the significance of glycine and its supplementation in body composition.
“It also can take in from food about another two and a half to three grams.”
Glycine's Holistic Health Benefits
31:02 to 33:18
Discussion on glycine's role in health, longevity, and glutathione synthesis.
“Well, Matt, I'm going to miss you when you're gone.”
Research Insights on Glycine
33:18 to 35:38
Explore various studies on glycine's effects on aging and health outcomes.
“Well, it's actually interesting to go on.”
Lifespan Extension in Model Organisms
35:38 to 40:50
Discussion on glycine's impact on lifespan in worms, flies, and mice.
“Okay, so let's get back to the primary focus of this episode, which is glycine, of course.”
Comparing Glycine and Betaine
41:00 to 42:04
Understanding the differences and benefits of glycine and betaine supplementation.
“As long as we're on the subject of glycine, I'd like to talk about a methylated amino acid that a lot of people think is very similar because it's got the word glycine in it.”
Exploring the Benefits of Trimethylglycine
42:04 to 44:16
Learn about the potential effects of trimethylglycine and glycine on exercise performance and health.
“It can even increase power in certain exercises, such as small upper body muscle exercises.”
Glycine and Its Longevity Potential
44:16 to 46:29
Discover glycine's role in collagen production and its promising effects on longevity.
“He's got his PhD, and he's done his postdoc with me.”
Glycine Dosage and Recommendations
46:29 to 47:17
Understand the importance of proper glycine dosage and consulting with a doctor.
“We know this because it even extends mouse's lifespan.”
Transcript
Automatic transcript. May contain errors.0:00In fact, this molecule has been around since the dawn of time.
0:02Dr. David Sinclair:Even before life, glycine is a mysterious molecule. And by giving more glycine, you actually can make more collagen. I think for the skin, taking glycine might actually help because it does improve collagen synthesis. It does extend the lifespan of many animals. We always want to look for that. And what they saw was really quite remarkable. Across the board, many of the hallmarks of aging were reversed. Glycine appears to improve memory in middle-aged adults. Glycine improves stroke recovery. Glycine was associated with an 11 % reduced risk of heart attack. So even if you're fit, it seems it can make you even better.
0:34Dr. David Sinclair:Incredible. Welcome to Lifespan, a show where we discuss the cutting-edge science of aging and how to live healthier at any stage of life. I'm David Sinclair, a scientist and professor working on understanding why we age and discovering new ways to slow and even reverse the aging process. On this show, I share an insider's look at the latest from my lab, the field, and what's just around the corner.
1:13Dr. David Sinclair:Want to know what's the best sweetener in the world? Glycine might be a contender, and its sweetness is only part of the story. Welcome back to Lifespan. Today, Matt and I explore a simple amino acid that helps build collagen, supports our antioxidant defenses, and has extended lifespan in some mouse experiments. I spent years studying this amino acid during my PhD. It was about 30 years ago, I admit. I never imagined that I'd come back to it as a longevity researcher or that the story would lead to NASA and microbes that survive in extreme environments. I consume glycine a lot. pretty much every morning I'm putting it into my drinks just for sweetener and I do find that I sleep better at least.
1:56Dr. David Sinclair:So today we're going to explore what the evidence says about how this differs from trimethylglycine or TMG, also known as betaine, and whether glycine could reproduce some of the benefits of restricting methionine and I get Matt to try it on camera which is something that's quite the challenge. I'm so excited to share that Lifespan magazine is now available, along with everything we're building around it to help you live a longer, healthier life. You'll get the gorgeous 100-page magazine, early access to Lifespan episodes, my longevity newsletter, clinical trial updates, AMAs, exclusive interviews, and a lot more to come.
2:34Dr. David Sinclair:Go to Lifespan.com to read the magazine, see what we're building, and support medical research too. There's a free version, an$8 a month membership, and a founder membership with lifetime access to the magazine, bonus material, and some personal gifts from me. Life's too short. Let's change that together. Okay, let's go. Welcome back to the LifeBand podcast with David Sinclair. I continue to be Matthew LaPlante. This guy here continues to be Dr. David Sinclair. How you doing, Matt? I am excellent. Well, today we have a really interesting topic we're going to cover. We do. We are going to be talking about an amino acid called glycine, which you have a very long and distinguished relationship with.
3:20Dr. David Sinclair:Yeah, it's a love-hate relationship, mostly love. And it turns out it's the most basic of all the amino acids, and it turns out to be relevant to aging and longevity. And if it was not for this amino acid, you actually would be doing something very different in your life, right? True. If it weren't for glycine, I'd be dead. Probably within 10 seconds. That was not the point I was trying to make, but that's a good point. You need this. Well, it's a conditional amino acid. You don't need it needed, right? Fair enough. You can generate it from serine, which is a slightly bigger amino acid. But yeah, I did my PhD on the catabolism, the processing of glycine in yeast cells.
4:00Dr. David Sinclair:It gave me the PhD I needed to head over to America and do some stuff on aging. And now, all these years later, it's almost 30 years later, almost, you are professor and lab director in the Department of Genetics at the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. That remains true. And the author or co-author of hundreds of research journals on the molecular underpinnings of our health and well-being and aging processes. Right. And you are not only my co-host here, you're also an academic at the Utah State University. For the moment. And co-author with me on the book Lifespan.
4:38Dr. David Sinclair:Which was a joy to write. What I wanted to do with this book was to explain why we as humans are so messed up biologically, physiologically, mentally, and why this world that we've built is just so bad for us. and how can we fix it? How in everyday life can we get through this society we've built, which feels great for a lot of us, a lot of food, don't even need exercise. Our suitcases even have wheels on them now, but that's not good for us. So what can we do every day to get through and even teach our kids to have a longer, better life? And one of the things that we can do is supplementation.
5:13And one of the supplements that a lot of people are taking right now is glycine. Do you like how I brought that right back around?
5:18Dr. David Sinclair:Yeah, I forgot why we were here. Well done. And so before we hit on glycine supplementation, I wanted to go back to a key concept that you often hit on. And people who have read Life Beyond the Book or people who've watched previous episodes, this is going to sound familiar to them, but it's an important concept. These three key longevity pathways, Sirtuin activators, mTOR inhibitors, and AMPK activators. All three of these make sense in the context of something that you have called the survival circuit. Can you hit on that briefly? Yeah, we came up with this during discussions for Lifespan, the book.
5:53Dr. David Sinclair:And the idea is that if we're in periods of adversity or even perceived adversity, we can trick our body into thinking we're going to die, but we're not really. By fasting, by exercising, by being in different temperatures, by taking molecules in from plants that are stressed, these give us the feeling of biological stress called hormesis. And the survival circuit exists to react to that and keep us alive. And it's been around pretty much since life first formed on the planet. We know this because survival enzymes are what we call longevity genes that give rise to these enzymes. We find them in plants, even in bacteria.
6:28Dr. David Sinclair:Of course, we have many of these genes in our own body, and we think that they've evolved to keep us alive when times are tough. Problem is, life's pretty easy these days for most of us on the planet, and these survival circuit genes just don't get turned on the way they used to. And so we age more rapidly. Most of the things that do turn on the survival circuit in that really positive way that leads to better health and longevity, as you've described it to me over the years, these things work together to either activate sirtuins to inhibit mTOR or to activate AMPK. And again, people can do a deep dive on that in the book, but those are the three things.
7:05Dr. David Sinclair:Yeah, I'll cover it very briefly. So Sirtuins, these are the genes that I worked on pretty much my whole career since I came to MIT in 1995, discovered a link to lifespan under Lenny Garanti's tutelage, where I was lucky to land, and that was in yeast cells. So sirtuins are silent information regulators, SIR in the name, and they regulate many different things. But what they do that I think is most critical is they stabilize the information in the cell, the DNA, the genome, and the epigenome, which we've talked about a lot because it's central to the information theory of aging, which I believe explains a lot of aging itself.
7:41Dr. David Sinclair:So there's the sirtuins. So we want to have more sirtuins, more those enzymes in the cell, or activate them with plant molecules or exercise or fasting. That's one set. The next one out of the three is mTOR. The body can sense when there's not enough amino acids around, particularly amino acids that are found in abundance in meat. So this is leucine, isoleucine, valine. These are called the branched chain amino acids. And they tell the cell, hey, there's a lot of energy, a lot of amino acids around. Go forth, multiply. And the body is in an abundance mode rather than this adversity mode. And so what we want to do, at least part of the time for longevity, is to reel that in, to make the body think that there's not enough of these amino acids around.
8:25And inhibiting mTOR does that.
8:27Dr. David Sinclair:Exactly. So that's right. You want to bring down the levels of amino acids, just occasionally so that the body thinks that it's suffering for a lack of food. And the problem is today we're eating tons of food and tons of meat. So the body doesn't ever turn down its mTOR and go into this survival mode, which is basically a fasting mode that recycles old proteins, and that's very healthy. One way to do that is to reduce the amount of branched chain amino acids. So I'm on a vegan diet now, and that reduces the activity of mTOR. You can also do other things. You can fast, and that also down-regulates mTOR.
8:59Dr. David Sinclair:Another way to do that is to restrict one amino acid that's relevant today, which we'll get to, called methionine, and that's another amino acid that the body can sense as to how abundant food is. Third one is called AMPK, and it stands for AMP, which is a chemical, activated kinase. And when you have a lot of AMP around, that means that the body doesn't have enough energy. So when you eat a lot of sugar, you've got a lot of energy, and AMPK levels go down. If you're hungry, you don't have enough energy, AMPK levels go up. And you can also boost AMPK with drugs, such as metformin, But you can also exercise, which is one of the best ways to increase your AMPK activity.
9:39Okay. So most longevity extending strategies that we have covered before, they either activate SIRTOWINS or they inhibit mTOR or they activate AMPK. But increasingly, what we're seeing is that many of these interventions actually do all three of these things together.
10:00Dr. David Sinclair:They do because one component will activate or inhibit the other. So for instance, if you raise NAD levels and activate these sirtuins, that will also activate AMPK and downregulate mTOR. And they're all talking to each other. So you don't always have to do all of these interventions or these lifestyles at once. You do one or two of them and the rest will be taken care of. Yeah. Okay. One of the examples of this is caloric restriction, which activates AMPK. It inhibits mTOR. It increases NAD +, which activates sirtuins. Exercise does this too. So does metformin. Metformin does all three of these things as well, correct?
10:38Dr. David Sinclair:Right. Metformin is really interesting. But what we know is that metformin will inhibit respiration and lower energy in the cell. The mitochondria, the power packs have lower ATP, and the AMP goes up. So AMP is now going to activate this AMP kinase, AMPK, and you get all the lovely benefits. So metformin seems to be very helpful for longevity, at least diseases of aging at a minimum. And that seems to be how it works by initially lowering the energy in the cell. And the reaction to that, again, hormesis is, holy cow, we're running out of energy. Let's make more energy producing mitochondria and you get the benefits.
11:15And then it also inhibits mTOR.
11:17Dr. David Sinclair:Yeah. And it activates the sirtuins and they all go up and all three of these pathways are now doing what they should. Often it's asked, well, what are these genes actually doing? Oh, it's pretty complicated. There's a lot of things that these pathways do. Generally, they counteract the hallmarks of aging, of which there are about 12. Just to list a few, mitochondrial decline, misfolded proteins, of course, changes to the epigenome, which we work on, senescent cells, inflammation. These are all things that seem to be dampened in a positive way by these pathways. This sort of trifecta effect is so common now that we really expect it to be the case.
11:56When we see an effective lifespan and healthspan extending intervention, it almost always fits into one of these three pathways.
12:04Dr. David Sinclair:Or we try to force it. Or we try to force it in, which is interesting because today when we get to glycine, it's sort of a mystery. Glycine is a mysterious molecule. It doesn't easily fit into one of these three pathways like most of these other things we've talked about. Glycine, for instance, doesn't affect sirtuins, as far as we know. It downregulates AMPK, which is the opposite of what you'd expect. And when you throw it on cells, even mTOR is boosted, which is anti-longevity. So all of that's a bit mysterious, but we have dug in with our research team and we have some ideas how it's actually working, which is non-obvious.
12:39So glycine's a bit of a mystery, but it's not a mystery for lack of trying to understand it. In fact, this molecule has been around since the dawn of time. Even before life. Yeah, they found it on a comet or something, right?
12:51Dr. David Sinclair:Yeah. It's found in the universe and then we've used it to make proteins but at least to our knowledge we've known about it since 1820 this guy henry breaknaut my french-speaking daughter would definitely cringe she'd be like it's reckon this reckon oh yeah yeah and so he took gelatin which is mostly collagen and boiled it with acid right and yeah this guy was like trying to come up with different ways to make sugar by using sulfuric acid and just burning things with sulfuric acid So he made wood sugar, and he made straw sugar, and he made cotton sugar, and then he made this thing. You might say he had a sweet tooth.
13:29Dr. David Sinclair:You could say. And he named it. Actually, originally, he called it sugar of gelatin in French. It was then changed to match other amino acids to glycine derived from the glycous, a Greek word for sweet. Nice. Yeah. It's a fact you always wanted to know. It is. Or afraid to ask. then it's been played around with a lot since then by people who are just trying to figure out what is this sweet little powder good for. One thing that's important to me is that Lifespan only partners with companies that I genuinely believe in. They must be grounded in science and willing to support medical research that will ultimately change how we treat aging and diseases.
14:08Dr. David Sinclair:Their support also helps keep this podcast free for millions of listeners around the world. One of those companies that I'd like to mention is Ketone IQ. I've known the founder Mike for over five years and I'm a huge fan of what he's doing. I've been studying the benefits of fasting for over 25 years now. And one of the most important molecules is beta-hydroxybutyrate or BHB, the primary ketone that our bodies make during fasting. That's an important metabolic fuel for your brain and your muscles. More recently, science has shown that BHB is also an epigenetic regulator of your immune T cells.
14:42Dr. David Sinclair:These are cells that protect against viral infections. Ketone IQ is a little shot that contains R13-butanediol, a naturally occurring molecule that your liver converts into BHB. And it happens in minutes instead of the day or two it normally takes through fasting. One of the studies on BHB that caught my attention recently was by Stephen Kornane and colleagues. Their work in 2016 showed that while the aging brain loses its ability to use glucose efficiently, its ability to use ketones remains largely intact. And more recently, Quinoneus and Blammon published a randomized trial in 2022 in the journal Nutrients, showing that ketones help preserve reaction accuracy during prolonged mentally demanding exercise.
15:28Dr. David Sinclair:Personally, I use ketone IQ quite often when I have a long day, when I'm recording podcasts, I'm writing, or I'm feeling a little down, or maybe getting a virus, I'd love you to try Ketone IQ too. I asked the guys at the company to offer a 30 % off discount for your first monthly order, which they kindly agreed to. You can visit ketone.com slash lifespan, or at the checkout, just use the code lifespan. Yeah, well, if anyone's wondering what it looks like, we have a drawing of it. Andrew can throw that up on the screen here. It's very simple, It's just got a couple of carbons there, a nitrogen and two oxygens.
16:08I made one for you. Yeah. Doesn't it look like a Jeff Koons statue, though? The balloon dog?
16:12Dr. David Sinclair:Well, it needs to be about six foot tall. But yeah, that's beautiful. So there you see there's the nitrogen, the two carbons and the red oxygens there. So it's the simplest amino acid. And, you know, if meteorites can make it, it's got to be simple. So let's fast forward now to the 1990s. As we said earlier, this amino acid was a big part of your dive into genetics. That was in Ian Dawes' lab at the University of New South Wales. Before we get into that, though, I need to go down a little bit of a rabbit hole here. Because while I was preparing for this episode, and I should say I've known you now for a long time.
16:46I even helped you write a book that is at least part biography. But when I was investigating your work in Dawes' lab, I read something that I did not know about you. I don't even know if it's true. Somebody else wrote it. Did you try to start an abalone fishing company before you were in Dawes' lab? Like you had done this graduate work and then you tried to fish for abalone?
17:10Dr. David Sinclair:Well, I didn't want to be in a lab my whole life. So I thought in the great outdoors, I had some training in marine biology. I was a scuba diver and a windsurfer. Okay, so that doesn't happen. You wind up working for Ian Dawes at the University of New South Wales. What made glycine so interesting to you and Dawes back then? Well, put simply, we're trying to understand how genes were regulated, and yeast cells were a good way to do that because they're very simple. In those days, doing genetics in human cells wasn't really feasible. We didn't have CRISPR or anything like that. So yeast cells was it.
17:44Dr. David Sinclair:That was the high technology. We didn't even have a genome of a yeast cell yet, so you had to find genes. And one of my projects was to find the genes that allow the cell to utilize glycine. and then understand how do those genes get regulated by glycine. And that could tell us how cells work. And I found the three genes that are necessary to process glycine as a carbon source. And it took me about a year. And then I finally sequenced the genes. Sequencing in those days, by the way, was very different. We used toxic chemicals. We had little thin plates between long glass sheets that were a foot or more long.
18:21Dr. David Sinclair:High voltage, super dangerous. and then you get maybe 150 letters. And that took me three months to read the code of those three genes. And it was a milestone. I got a PhD from it. These days, you can read a million letters in an afternoon on a device that's the size of a Twinkie. Long story short, I got a PhD, thank God, and then headed off to the US to do something more interesting. And you were still working on yeast, but you were no longer at that point working on glycine. but almost 30 years since these findings, your first paper on glycine was published in 1995. It still gets cited today.
18:58Dr. David Sinclair:Amazing. So what it did really for me and for my work since was give me a really good background in genetics and biochemistry and all this stuff. It was my training ground. Little did I know that glycine itself was going to turn out to be a longevity molecule. And that brings us back up to speed on why we're here today, because glycine has been shown to be highly effective across many different areas of health. It has been shown in model organisms to extend lifespan. There are three ways that you've said this might be happening. Maybe all three of these are working together, but let's go through them one by one.
19:36Let's talk about glutathione.
19:38Dr. David Sinclair:Yeah, glutathione is what's called a tripeptide. It's got three amino acids, glutamate, cysteine, and glycine. And it's an antioxidant that is found throughout the body. It's needed to protect the tissues. The liver is particularly important for that, where it makes a lot of glutathione. If you don't have it and you drink alcohol or take acetaminophen, you can have real damage. And it's thought that maybe by supplementing with glycine, and occasionally some people have tried glycine plus a source of cysteine, an acetylcysteine, that you get loads more glutathione, and then that helps protect the body.
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20:10Dr. David Sinclair:And that's why you see these health benefits. That's theory one. Okay. So that's theory one. Theory two has to do with our skin. Well, collagen is the major source of glycine. Remember, that's where it was derived from gelatin. And our bodies have to make collagen all the time. In fact, it's been calculated that we have a deficit of collagen because we don't make enough, especially when we get older. And by giving more glycine, you actually can make more collagen, which might help the tissues. issues there's a twist on that and the degradation products of collagen which is a hydroxyl prololated glycine which is a modified glycine can actually act as a signal itself to turn on mTOR which can help cells divide and that might heal things and make things better i'm not so sold on that theory itself but i think for the skin taking glycine might actually help because it does improve collagen synthesis.
21:00And this relates to skin health. We're talking about our largest body organ and the protective casing for the rest of our body. So anything that you can do to help that organ do its job, which is to protect us from injuries and disease, is going to result in better long-term health. For sure.
21:20Dr. David Sinclair:And collagen is needed not just for the skin, but all tissues needed to be held together. So it's not going to hurt you to have more collagen. but I don't think that that would be enough to explain all of these health benefits. And that brings us to the third one, which is that glycine appears to mimic the restriction of methionine, which is one of these important amino acids that we were discussing earlier. And that's going to get us back to a place that we were at the beginning of this episode. But first, what I want to talk to you about is how does it do this? How does glycine act as if methionine is being restricted in our bodies.
21:57Dr. David Sinclair:Well, I really like this theory. It was proposed initially by Adiv Johnson, who used to be a researcher on this podcast for season one. Shout out to Adiv. Adiv, good job. And so what he's proposing is that glycine needs to be catabolized. So either converted to energy or gotten rid of if there's an excess. And actually, if you take enough of it, three to five grams, we'll get into the dosing later. The body puts a methyl on it. The same chemical that we now know goes on DNA, methylated DNA, the clock of aging. So methylated glycine, which is catalyzed by an enzyme called glycine N-methyltransferase, which basically transfers methyl onto the glycine, that tags the glycine to be excreted.
22:40Dr. David Sinclair:So if you take a lot of glycine, you'll find this product, methylated glycine, in your urine. It's called sarcozine. You can pick it up on a blood test. Normally you don't have any in there, but people like me who take a lot of glycine, that'll be excreted. And what's interesting about that is that methionine is used for that reaction. And so S-adenazylmethionine is a chemical that is catalyzing that reaction. And in doing so, you destroy methionine. So what I believe is going on, and I think Adiv is right, is that when I take gram quantities of glycine, the body has to use methionine to get rid of it.
23:13Dr. David Sinclair:And that way, my body is slightly deficient in methionine. And I think what's happening is my body gets to think, oh, goodness, I'm running out. Oh my gosh. I sound very Australian or British, don't I? Oh my crikey. Headless to Betsy. My body is deficient in methionine and it down regulates mTOR and I get the health benefits of a body that's in adversity mode rather than abundance mode. This is pretty cool because methionine is necessary. We find it in red meat and fish and dairy, legumes. But even though it's essential, a lot of people get way, way too much of it. and it's been implicated in all sorts of health conditions.
23:52Too much methionine leads to heart disease, oxidative stress to endothelial cells, stroke, cancer, dementia, all sorts of bad stuff. So we need less of it anyway, but we do need some of it. But through this process that Adiv has described and that you think is going on, we can still get healthy levels. We probably shouldn't extend those levels with all this red meat eating, but we can still get healthy levels of methionine, but have the body think that we're not getting methionine.
24:21Dr. David Sinclair:Exactly. And you've got to be careful about this, right? Well, of course, you don't want to be chronically deficient in methionine either. You have to make sure you take the right amount of glycine if you try this and monitor it with your doctor's supervision. And we just don't like pop those pills like crazy. Well, sometimes what I hear is, you know, if one gram is shown well to work in a clinical trial, someone will take 10 thinking it'd be 10 times better. So don't do that. Yeah, that's bad math. Yeah, stick to what's currently known as apparently safe. That's a disclaimer. You know, glycine, actually, it's worth mentioning.
24:52Dr. David Sinclair:Glycine is one of the safest molecules that we know it's been taken for decades, even in high quantities, and does extend the lifespan of many animals. But always be careful. There's nothing that's perfectly safe. Even if you drink too much water, it can kill you. And if glycine is mimicking methionine reductions, methionine deficiencies, what it's doing is mimicking this process that one of your friends and former colleagues has studied quite extensively this is work that comes out of dudley lambing's lab oh yeah so dudley to me is still a student he's now a very famous professor but he did his phd in my lab we looked at the sirtuin's ability to control caloric restrictions effects in yeast cells and he got a couple of really good papers one in science and he's gone on to do great things and one of the things he is doing in his lab is understanding how amino acids, either in abundance or in restricted amounts, affect lifespan and health span.
25:50Dr. David Sinclair:And he fairly recently showed that by restricting methionine, you get really big effects on metabolism and health in the same way that you would if you were exercising. But these mice were actually just sitting around in the cage, not doing any exercise. Yeah, I think he called it the couch potato mice study. or yeah that was a good name these mice they had their methionine restricted and they went from a normal dose to a very very small dose just like as much as they needed to survive and then they kept eating as much as they wanted they didn't exercise at all but they still had this huge fat reduction like 70 and then there have also been human studies that have shown that at least in obese adults restricting methionine increases fat oxidization and it stimulates autophagy, which is the recycling of old proteins that usually is happening when you fast.
26:43And also is related to several of these pathways. Right. That we were talking about earlier. Yeah.
26:51Dr. David Sinclair:And so this is methionine restriction. Right. Which is, we believe, caused by taking a lot of glycine. And here's where things come back around because methionine restriction has been shown to down-regulate protein synthesis, activate AMPK, reduce mTOR signaling, and up-regulate SIR. So methionine restriction, which is this thing that glycine mimics, does the things that we would expect to see for longevity interventions. Yeah. And what I suspect is going on is that the studies that show that glycine didn't have these effects, these are short-term experiments. But chronically, you get this methionine depletion, which takes a while, doesn't happen within hours.
27:31Dr. David Sinclair:And that's what gives you the longevity benefits. So the prediction, if this model is correct, is that taking large amounts of glycine should mimic the effects of methionine restriction. And that's exactly what is being shown in animals and now in people. When we say large amounts, you said don't take 10 grams because one gram is sort of like that spot that a lot of people are taking, correct? Some people take more. What's interesting is that it's been calculated that the human body makes about three grams a day. Okay. It also can take in from food about another two and a half to three grams. But to make all that collagen, especially an older person, they would need to supplement and get it up to about 10 grams.
28:10Dr. David Sinclair:So there's a deficit. it. And so perhaps by taking this extra glycine, you're also meeting the body's needs. It's not so much of an excess anyway. A few months ago, after a lot of travel and speaking engagements and probably too many dinners out, I realized I'd put on a few extra pounds and I could see the graph on my withing scale and I needed to shed a few. My goal, however, was not to simply lose weight. I wanted to get back to my usual body composition. Had I lost muscle? Was my visceral fat creeping up? What did I need to focus on? That's why I like the Withings Body Scan Scale. It tells me much more than my weight.
28:49Dr. David Sinclair:It measures body fat, muscle mass, visceral fat, and even includes an FDA-cleared ECG. As I made a few changes to my diet and got back into my normal routine, I could actually watch my body fat come down while preserving my muscle. And that's far more useful than watching a single number on a scale. I've actually been using Withings products for well over 10 years, and lately I've become a big fan of their watches as well. They continuously track heart rate, sleep activity, temperature trends, and even blood oxygen. I wear the Withings Silver ScanWatch Nova, which looks a lot like an expensive diving watch.
29:26Dr. David Sinclair:Withings also makes one of my favorite blood pressure monitors for home use. Also a sleep analyzer that can help identify sleep issues and have a smart thermometer as well. If you'd like to build your own health lab like I have, visit withings.com slash lifespan for 10 % off your entire purchase. All right, so glycine as a memetic may be having the same effect. In other words, it's allowing our bodies to have this essential amino that we need while tricking it at the same time into perceiving adversity. And if that's true, then that may be the reason why the literature is just so replete with examples of glycine leading to all of these holistic health and longevity impacts.
30:11Dr. David Sinclair:Yeah, if it's true, we're certainly lucky because glycine's really cheap. I think it's 25 bucks for a kilo or something. And it's seemingly very safe. And it's sweet. And it tastes good. And it tastes good. And actually, you don't like pop it as a pill. you actually sprinkle it on stuff as a sweetener, right? Sometimes, depends on how I feel. But yeah, it's nice so I can drop it in my tea or just put in some water. I have some here. Do you want to try it? Yeah, yeah, absolutely. One up here. Here's a... Here's a capsule. How do I even know that you know what's in here? All right, for those who are not watching the video, this is a white powder.
30:47Okay.
30:48Dr. David Sinclair:All right, I'll have a taste here. All right. It is like a really weak sugar. it's really good that it's a little bit crunchy well if you told someone it's sugar they probably believe you yeah i drink coffee as you know a lot of it and you do this in coffee i'm sure you can well the heat for my coffee going to like make it less bioavailable or anything like that no it dissolves easily oh you just put it in your cup yeah nice yeah my mr rogers cup oh so you're gonna start taking glycine every day no i don't think so i don't think so you haven't convinced me to do any of these things every day. Well, Matt, I'm going to miss you when you're gone.
31:28I love that line. So let's note here before we kind of like drop into talking about the human studies that many of these studies are on Gly-NAC, glycine, N-A-C. And the reason for that is that one of the outcomes that people are going for when they're supplementing with glycine is glutathione synthesis, which you mentioned earlier. You can't make it with glycine alone. You also need cysteine, which is an amino acid that has sulfur in it.
31:58Dr. David Sinclair:Bet you didn't know that. I did not know it had sulfur in it, but I did know that you can't make it with just glycine. You have to have N-acetylcysteine or something that provides cysteine. But in this case, that's what they use the NAC for. Right. So glycine has been shown in animals and people to have benefits, but it seems to be enhanced when you add this NAC, N-acetylcysteine. And that brings us to this paper that we really want to talk about. And it looked at young adults and some older people too, and looked at if people took 100 milligrams per kilogram of body weight per day. So if you weigh 70 kilograms, you would take seven grams every day.
32:34Dr. David Sinclair:And what they found was remarkable. I'm sitting here trying to do the math in my, you know, imperial measurement brain, and it's not working for me. Yeah, well, I'm Australian. I can do these. No worries. So this study, even though it was a small number of people, they had a placebo control, which was nice. We always want to look for that. And what they saw was really quite remarkable. Across the board, many of the hallmarks of aging were reversed. They showed improved glutathione deficiency. As you'd expect. Right, because that's the first thing you're going for with the Glynec, right? That's a biomarker, yeah.
33:07Okay, yeah. Improvements in oxidative stress, reduced mitochondrial impairment, reduced inflammation, reduced insulin resistance. The list goes on.
33:18Dr. David Sinclair:Well, it's actually interesting to go on. Physical function and strength increased. They had less waist circumference. Blood pressure improved. This was all in 16 weeks, by the way. Incredible, right? Okay. Now, normally we would see study results like this. We go small group, right? Really small trial, short term, 16 weeks. It's just one study. This would be like insane to believe this if it was just a single study. But this comes on top of scores of animal research studies showing similar effects, lots of human trials and cross-sectional human studies that have shown really interesting associations between glycine and other health outcomes as well.
34:00Dr. David Sinclair:In animals, lifespan extension, improvements in body weight, there's a lot of work on that. And in humans, type 2 diabetics had 5 grams a day. Within a matter of weeks, they had less inflammation and better blood sugar levels. So this is, like you say, one study doesn't really prove anything in science, but when you see it time and time again in different species and in humans, you've got to start to say something is interesting going on here. Yeah. Do you want a non-exhaustive list here? I can tick these off really quick. So let's go back to almost back when you were working on glycine. Okay.
34:321999 in the UK, a study shows that glycine appears to improve memory in middle-aged adults. The next year, 2000 in Russia, glycine improved stroke recovery. 2012 in Germany, higher serum glycine concentrations were associated with a reduced risk of impaired glucose tolerance. 2015 in Norway, this is a study of 4 ,100 people over seven and a half years. Plasma glycine was associated with an 11 % reduced risk of heart attack. 2017, Canada, that's the type 2 diabetes study. Type 2 diabetics have lower levels of serum glycine. In 2017, your home country of Australia, glycine protects muscles during different wasting conditions.
35:11And on and on it goes.
35:14Dr. David Sinclair:And also in animals, there's evidence as well. And actually I have a better idea of what's going on because you can now manipulate the genes in these animals. And there's one gene that, remember, methylates the glycine to get rid of it and deplete methionine. That gene GNMT, when you upregulate it, you actually get lifespan extension. For example, in flies, you get a longer lifespan and lower methionine levels, all consistent with this theory. Okay, so let's get back to the primary focus of this episode, which is glycine, of course. We've been talking throughout this episode about all of these sort of like individual health effects.
35:49And cumulatively, what you see is this real holistic health benefit from glycine and often glycine, Glynax supplementation. But we haven't really talked about the longevity, the potential longevity benefit. And one of the things we should say here is, as we always say, longevity studies in human beings are very difficult. But there's been a lot of work on this in model organisms, rats and mice. and it is every bit as impressive, I think, as the results that we're seeing from a lot of the other molecules that have been applied to model organisms to extend lifespans. So you want to talk about some of those studies?
36:29Dr. David Sinclair:Let's start with simple organisms. Simplest being a worm. In this case, if you feed them glycine, they live about 10 to 20 % longer, which is nice. But it's a worm. It's a worm. So let's work our way up to fly. So, a fly, what they did was they overexpressed, turned on the gene for GNMT. You'll recall this is the gene that allows the flies to convert glycine into methylglycine to get rid of it. So, they weren't giving them glycine. They were tooling with the gene instead. Right. So, they weren't just giving them glycine. They were actually doing something more interesting, which was they were turning on the gene, giving them more of the gene that turns glycine into methylglycine, thereby getting rid of methionine.
37:09Dr. David Sinclair:Okay. Going back to the original thing we were talking about. And when they did that, that was sufficient, just changing this one gene, upregulating it, extended lifespan by about 10 % in males and female flies. So we got about 20 % of the worms, 10 % on the flies. So we're seeing benefits in both of those organisms. That leads us, I assume, up to mice next. Let's go to mice before we get to rats. One group that did this is the ITP, the Interventions Testing Program, run by Richard Miller and Randy Strong. And they found that across three different universities, they could get reproducible lifespan extension in these mice.
37:39Dr. David Sinclair:These are outbred mice. So this is not just one inbred line. So it's very believable. And they found that in females and males, there was lifespan extension of four and six percent respectively. So that's super rigorous. That was 2019. And that was glycine alone. And then there was this other study in 2022. This one was out of Baylor that showed the Glynax supplementation increased lifespan by 23 percent in female mice and 24 percent in male mice. That was a huge effect. And they found lower levels of oxidative stress and improved SIR3 levels. So SIR3, one of the sirtuins. And they could even find increased genomic stability.
38:18Dr. David Sinclair:So DNA repair was upregulated. So all good stuff. And that 23 % is similar to what you get with methionine restriction. Again, consistent with this theory. But the one that I think is the most impressive is this rat study that came out very early on in 2011 that showed that glycine supplementation can mimic methionine restrictions. I think they were the first ones to propose this. And they found up to 28 % increase in mean lifespan and 31 % in maximum lifespan. That's an impressive result. Okay, so across a lot of model organisms, we're seeing a lot of lifespan benefits. we don't know what that looks like in humans but we know it improves health we know what it would we do know yeah we do know in individual health outcomes what it looks like in humans we don't know yet on that sort of like macro lifespan level true but it is consistent with a lifespan extending molecule if you see lowering of blood pressure body weight increased energy these are all consistent with a lifespan extending molecule as a scientist i like measuring things rather than guessing.
39:23Dr. David Sinclair:Which brings me to a science-based wearable that I'm particularly fond of. Of course, I'm talking about the WHOOP band, the one that I rarely take off. WHOOP continuously tracks my sleep, my resting heart rate, my heart rate variability, respiratory rate, daily strain and recovery, and other aspects of my health, giving me objective data about how my body is responding to the changes that I make. On weekends, you'll usually find me on Cape Cod, in my workshop or outside on the property, planting fruit trees, repairing the house, or hauling lumber in my old 1992 Ford F-150 pickup. Sometimes, however, I wake up eager to get outside, but my WHOOP tells me a different story.
40:02Dr. David Sinclair:My heart rate variability is lower than usual, my resting heart rate is elevated, and my recovery score is really poor. So on those days, I still head out, but I pace myself. I found that listening to those signals helps me recover better and work harder over the long term. I appreciate that WHOOP is backed by great science. For example, in 2022, Miller and colleagues published a study in the journal Sensors comparing six leading wearable devices against clinical grade measurements of sleep, heart rate, and heart rate variability. WHOOP was among the most accurate for measuring overnight heart rate and HRV.
40:37Dr. David Sinclair:These are the two biomarkers that I pay close attention to because they provide valuable insights into recovery and physiological resilience. So if you don't already use Whoop, I really encourage you to give them a try. So visit join.whoop.com slash lifespan, and you can use the code LIFESPAN to receive your free Whoop and your first month of membership. As long as we're on the subject of glycine, I'd like to talk about a methylated amino acid that a lot of people think is very similar because it's got the word glycine in it. It is different as the trinethylglycine, also known as betaine, right?
41:18Dr. David Sinclair:Yeah. Well, betaine, it was found in beets. That's where it gets its name. And it does a lot of things. It protects cells from oxidative stress. It also is required to make this other amino acid, methionine. But it became really popular in recent years because it was thought that when you take an NAD booster like NMN or NR, that it'll potentially deplete the body of these methyl groups. It's still controversial. There was a study about Parkinson's disease. Patients treated with NR, they saw no defect in the ability of the body to make and have enough methyl groups. I think it's pretty unclear, but nevertheless, betaine is an interesting molecule.
41:54Dr. David Sinclair:It does a lot of good things to the body, including to the skin. What are some of the advantages of betaine? Well, it has been shown to decrease homocysteine levels, which is a marker of cardiovascular disease risk. It can even increase power in certain exercises, such as small upper body muscle exercises. That was a 2010 study. There was another one that looked at VO2 max and sprint ability, and it went up in 29 pro soccer players. So even if you're fit, it seems it can make you even better. But interesting molecule, exactly how it's working, we're not sure. It's probably not through methionine depletion, the same way glycine works because it's actually, as I mentioned, helping make more methionine.
42:32Yeah. So you had mentioned to me off camera earlier that it's probably not a great idea to take trimethylglycine and glycine at the same time.
42:43Dr. David Sinclair:Well, I think so. We could test this, but given that glycine is probably mimicking a lack of methionine and that the trimethylglycine or betaine does the opposite, but probably they could counteract each other. So I would do one or the other. And given for myself, I'm taking glycine now, I'm not taking the trimethylglycine, the betaine. Is there a differentiator like why people would want to do trimethylglycine as opposed to glycine or vice versa? Oh, yeah, maybe. I think that weight of evidence on strength performance is on the betaine, the trimethylglycine side, but on the longevity and weight loss and metabolism, glycine seems to be the winner based on the science at this point.
43:21Dr. David Sinclair:Gotcha. Yeah. Okay. We should make a note about dosing here on TMG, on betaine. What are normal dosing amounts? Well, like any molecule that you take or might take in gram quantities, you have to be very careful. And one of the things that's known about betaine is if you go above four grams a day, you're at risk of having higher levels of LDL or bad cholesterol. So I would say don't go above that, even though some of these clinical studies have gone as high as nine grams a day. Are there also considerations for TMG, trimethylglycine, or betaine that is in skin creams? Because I know a lot of people like to slather on skin creams that have this stuff in it.
43:56Dr. David Sinclair:Yeah, so betaine has long been known to be good for the skin. In fact, a former lab member, Dr. Carl Landry, we've been working with NASA on a few little things. Carl's an extremophile researcher, right? That's right. Yeah. So he did his PhD on an organism that he discovered that can survive in super hot places. He also went down into the Earth's crust to collect organisms as well. So he's our bioprospector. But Carl's gone on. He's left the lab now. He's got his PhD, and he's done his postdoc with me. And now he's CEO of a skincare company. Because what happened was, when we were working with NASA, he actually, through conversations, discovered that NASA has freezers full of bacteria and fungi that have interesting properties, one of which could survive in outer space.
44:38Dr. David Sinclair:And he started studying that. and he found that this organism, which is Bacillus pumilus, could provide UV protection and he put that into a skincare line. And that's what became this cream, which also has trimethylglycine in it. He put betaine in there to give it some extra punch and it's now out there and people are loving it. It doesn't just provide UV protection naturally, but this bacterial extract seems to also activate the sirtuins and the betaine provides the protection of the skin cells. So this is one of the things that I've been putting on my skin for a while. And you're glowing. I'm glowing.
45:11Dr. David Sinclair:So Kyle, you can look him up. With NASA, we recently put out a publication that talks about Della v. Sciences, the product's called Aonia. And it's out there if anybody wants to try it. Okay. So we've talked about a lot of stuff today. What should people take away from this? What are the really main takeaways from this glycine conversation? So based on all this animal research and the more recent human studies that look really promising, I started taking glycine a few months ago. And so far, so good. I'm taking about two grams a day, which is not a high dose. I always start low and work my way up.
45:42Dr. David Sinclair:I'm, of course, working with my doctor, taking bloods to see if my body's doing okay, looking at my liver in particular. And so far, my blood work has never looked better. So, so far, so good. But again, every molecule that you take, you want to make sure that you're not doing yourself any harm. but given all of the data we've talked about, all of the science, glycine is not only one of the safer molecules, it really does look one of the more promising as well. So what can you take away from today's episode? Let's go through it. We now know that glycine is much more than a sweetener, though it is really great at that.
46:17Dr. David Sinclair:It helps us make collagen for our skin and glutathione for antioxidant activity and there's an intriguing possibility that it could mimic some of the benefits of restricting methionine, which shifts the body towards maintenance and repair, and possibly longevity itself. We know this because it even extends mouse's lifespan. It's early days, of course, but it's really promising. Small trials of Glynac, which combines glycine with N-acetylcysteine mixed together, that's shown strong and promising improvements in metabolic health and physical function in humans, though I don't take it as often as I probably want to because it does have a bit of a sulfur smell.
46:58Dr. David Sinclair:So glycine is just one supplement that you can take, but I want to remind you that it's still really important to exercise and eat well and get enough sleep, and certainly don't smoke. If you're considering glycine or Glynac, especially at high doses, please do talk to your doctor. More isn't necessarily better in this case. So that's it for another episode of Lifespan. Thank you so much for joining us. Don't forget to subscribe so you don't miss an episode and join us at Lifespan.com, where we give you the tools to live a longer and healthier life. Lifespan magazine is now available along with everything we're building around it to help you live a longer, healthier life.
47:39Dr. David Sinclair:You'll get the gorgeous 100-page magazine, early access to Lifespan episodes, my longevity newsletter, clinical trial updates, AMAs, exclusive interviews, and a lot more to come. Go to Lifespan.com to read the magazine, see what we're building, and support medical research too. Life's too short. Let's change that together. Lifespan is produced by Andrew, The Wonder Man Ying, Rajiv, Geek Me Out Ramesh, Marissa, who's on First Volgamoor, Kathleen, TLDR Fitzgerald, and our researchers, Shivani, Just One More Thing, Sethi, and Adiv, Meet Me in the Year 3000, Johnson. Also, I want to mention our new recruit, Daniel Rocketman Salazar, who's our new producer.
48:24Dr. David Sinclair:And of course, Serena, my honeypun. I also want to thank Inspiro Studio and Create Ape for making this show possible. And finally, thanks to our partners for helping us support longevity research. We'll see you next time.
48:45Dr. David Sinclair:This show is for informational purposes only and is not medical advice. Please consult a qualified healthcare provider as individual results may vary. Views expressed are my own and not those of Harvard University or Harvard Medical School. Full disclaimer is in the show notes.
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Could an amino acid sweet enough to replace sugar also help us live longer? In this episode, David and Matt explore Glycine, one of life’s simplest building blocks, and why it’s attracting attention in aging research. From building collagen to blood sugar control, heart health, memory, and recovery after stroke, its potential reaches surprisingly far. They unpack studies linking glycine to multiple hallmarks of aging and longer lifespans in animal models and ask what it would take to show these benefits in humans.
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The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program.
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