Sunday Science by GoUnPro 2026_08_02 Protein Restricted Diets

https://youtu.be/LxA7NHW7OlU

Insights on Protein Restriction and Longevity

Summary Of Speaker Contributions

Dr. Brent Laartz: Served as the primary presenter, synthesizing findings from over 300 scientific articles regarding protein restriction and its impact on aging. He highlighted the role of nutrient-sensing pathways, such as mTOR and GCN2, and argued that while high protein intake is often marketed for muscle growth, it may negatively impact longevity and metabolic health in older adults. He advocated for a plant-based, calorie-restricted diet coupled with consistent resistance training.

Offered a brief, critical observation regarding the British twin study, suggesting that the correlation between high protein intake and sarcopenia might be confounded by participants consuming more protein due to pre-existing medical conditions.

Key Points And Decisions

Nutrient Sensing and Aging: The discussion established that restricting protein—specifically branched-chain amino acids like isoleucine—deactivates the mTOR pathway, which is associated with accelerated aging. This restriction promotes autophagy and improves stress responses.

Sarcopenia and Protein Intake: Contrary to common fitness advice, the reviewed data suggests that high protein intake in older adults is associated with sarcopenia. The consensus reached is that resistance training is a more effective intervention for maintaining muscle quality than high protein consumption.

Metabolic Health: Evidence indicates that protein restriction enhances metabolic health, improves insulin sensitivity, and increases energy expenditure through the FGF21 pathway.

Dietary Strategy: The meeting concluded that a whole-food, plant-based diet, characterized by reduced red meat and simple sugars, combined with regular exercise and sleep, represents the most effective approach to healthy aging and disease resistance.

Next Steps And Action Items

Dr. Brent Laartz: Committed to providing the referenced research articles, including the University of Wisconsin review and the British twin study, in the show notes for further audience review.

Audience: Advised to conduct personal research and consult with their own physicians, therapists, or nutritionists before implementing any changes to their diet or exercise regimens based on the presented information.

Articles:

Mary Ni Lochlainn, Ruth C E Bowyer, Ailsa A Welch, Kevin Whelan, Claire J Steves, Higher dietary protein intake is associated with sarcopenia in older British twins, Age and Ageing, Volume 52, Issue 2, February 2023, afad018, https://doi.org/10.1093/ageing/afad018 

Knopf B, Lamming D. The hallmarks of protein and amino acid restriction in aging and longevityCell Press Blue, 2026; 0

Green C, Trautman M, Chaiyakul K … Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.  Cell Metabolism, 35, 1976-1995.e6

SPEAKER_0

 Welcome to Sunday Science, where we dive into a few recent scientific articles and their translation into our modern lives. Here is your host, Brent W. Lartz, M.D.

Dr. Brent Laartz

 All right everyone, welcome to another episode of Sunday Science. Here we're going to be talking about protein restriction. Really want to share this with you guys. I've seen this a little bit in some posts on social media about this review article. It really isn't really that much new news that no one has really brought out and reviewed quite yet in a comprehensive form of what protein restriction does in the concept of aging. So with the context of aging, protein restriction is Very controversial, right? Because so many people are espousing protein this, protein that, high protein diet, protein bars.

Dr. Brent Laartz

 Some of the gurus of anti-aging medicine are actually hawking their own protein bars out there because theoretically you would think that it would be important for us to have a lot of protein if strength and grip strength and thigh strength and lower extremity strength is important and you want to build muscle in older age, you would think that increasing protein would help. And there's been such a lot of data for carnivore diets and different diets that have high protein and weight loss. And part of that is the context of decreasing carbohydrates and therefore potentially improving diabetes. But There is data out there for protein restriction actually improving diabetes also. And obviously, those studies, if they are isocaloric.

Dr. Brent Laartz

 they're going to be replacing the protein in those animal diets and the human diets with carbohydrates, right? So hopefully it's not simple carbohydrates. And so that's where it is. So it is contradictory to sarcopenia and strength because in some of these weight loss diets and keto diets, et cetera, you do have potential sarcopenia. Again, some of that has been negated by some studies showing that these studies, if you, let's say, for example, the protein restriction, if you couple that with resistance training, you do not have the sarcopenia that you do normally. And certainly. Americans are sedentary, right? And so this is one of the problems for our world is that we have changed this to.

Dr. Brent Laartz

 the background here, have this little slide here, because this is schematically what is in this review article, okay? So we'll be talking about what's behind me in a second. All right, so it makes sense evolutionarily, though, because every... longevity study out there suggests that it is the nutrient sensing that activates mTOR and mTOR is the enemy of aging. Okay, so and we know that leucine and isoleucine, which are essential amino acids, increase mTOR. So mTOR then produces building of muscle. But mTOR is actually, you don't want mTOR activation, at least mTORC1, okay? So it makes sense evolutionarily because in a nutrient-scarce situation, you're going to have potential increased longevity because of deactivation of the mTOR pathway, okay?

Dr. Brent Laartz

 Sarcopenia can be overcome by resistance training. And think about potentially the sarcopenia that is found on some of these studies might be just... intramuscular fat that's actually decreasing and not necessarily just the muscle itself. It actually is quality muscle that is being built in patients who are losing weight as long as they're doing resistance training and as long as they are having a healthy, mostly plant-based. low protein, calorie restricted diet. Okay. So, but at the same time, mice are not humans. And these studies, even the mTOR studies and the aging pathways are preserved from the Drosophila, which is, you know, the Mediterranean flu fly to humans, those pathways and that longevity pathway is preserved.

Dr. Brent Laartz

 There's a reason why that pathway is preserved so well, because it works so well from even yeast cells. So when I say Drosophila up to humans, it's actually from yeast cells up to humans, from unicellular organisms all the way up to humans. There are Let's just talk about protein restriction here. You could restrict all proteins, or you could just restrict certain amino acids. And we've been taught forever that it's essential amino acids that our body can't make, right? So we need those in our diet. However, A couple of these essential amino acids, especially what we call branched chain amino acids, so that's valine, leucine, and isoleucine, may not be so essential after all.

Dr. Brent Laartz

 As long as you have some, we all need some of these branched chain amino acids to upkeep our protein levels. However, it may be that these actually... and especially isoleucine isoleucine is the amino acid and there are others that activates the mtor pathway okay so we'll talk about that in a second so we're going to be talking about three different One of these articles, not a groundbreaking article, but it is something that is contradictory to the sarcopenia argument, the protein restriction causes sarcopenia. All right, so let's talk about this article. So this article is the, and this comes from the University of Wisconsin, a guy by the name of Dudley, Dudley Lamming. Dr. Lamming is at the University of Wisconsin.

Dr. Brent Laartz

 He's had multiple studies showing the hallmark of protein restriction on aging and longevity. And most of his studies are in mice, but some of them are in unicellular organisms. And this study, so this is the review. We'll talk about the review first. we'll talk about another of his articles about dietary restriction of isoleucine and its effects on lifespan and health span of genetically heterogeneous mice. This was, that was in cell metabolism. This review we're going to be talking about is in cell press. And then we're going to be twin study in Asian Aging. So this came from 2023, not that new, but it shows the title of it is higher dietary protein intake is associated with sarcopenia in older British twins.

Dr. Brent Laartz

 Okay, so this study is a little bit contrary to some of the evidence that we have out there regarding protein, increased protein. and muscle strength and the inhibition of sarcopenia by a high protein diet. And I think this is an important contradictory study. Okay, so here's another one. Okay, so behind me, you can see. the evidence that they've laid out in this review. And I highly encourage you to pull this article, read the entire article, because it has layer after layer after layer. This isn't just a review of a couple of articles. This is hundreds of articles. This review article has, let's count

Dr. Brent Laartz

 references okay so this they've reviewed 361 articles to show this okay so the first we're going to talk about is nutrient sense sensing pathways okay we already talked about this a little bit in in the mTOR pathway we already mentioned okay so if you have a decreased protein levels in your diet. You have reduced mTOR activity, and that inhibits the growth pathway. It activates mK kinase, and it increases sirtuins, okay? So these, the sirtuins, are an important pathway for longevity, okay? So again, here, it's not only just a protein restriction, but certain amino acids decreasing these amino acids will do the same thing.

Dr. Brent Laartz

 Because as I said, isoleucine by itself and a few other amino acids by themselves, if you give a mouse these amino acids, they increase inflammation, they increase mTOR activity, and potentially increase muscle growth too. But that has an issue or a deleterious effect on aging. So if you decrease isoleucine, By 67%, we're going to talk about that article, then you decrease mTOR activity and you increase the longevity of at least the male mouse by 33%, the lifespan of that mouse by 33%. and the female mice by at least seven percent okay so um let's talk about some of these studies here so within some of these pathways so for example the mTOR if you if you have a mouse that has

Dr. Brent Laartz

 decrease inhibition of mTORC1, then you also lead to autophagy. And that's important, right? We've talked about intermittent fasting and, and time-restricted feeding, potentially leading to autophagy and decreased insulin secretion. There's also another pathway here, the GCN2 pathway. It's activated by an amino acid restriction, and that phosphorylates Some proteins that suppress eukaryotic initiation factor, selectively promoting the translation of activating transcription factor 4, and that is a key activator of stress response and autophagy genes. And they've found, for example, that Drosophila, lacking that GCN2, die when amino acids are restricted. So if you restrict amino acids, so this is very important, obviously, the deletion of that GCN2, it's very important for when nutrients are scarce. So, and.

Dr. Brent Laartz

 um deletion of that GCN2 in yeast blocks the ability of dietary restriction to extend lifespan so if you block that GCN2 and you have dietary restriction let's say caloric restriction caloric restriction for a yeast is obviously taking away the glucose or the food and that dietary restriction normally causes a yeast to live longer, but that lifespan increase is not there if you delete the GCN2 gene. All right. So obviously that makes that very important. So that's all we'll go into as far as this review, but there's a lot more on this.

Dr. Brent Laartz

 portion of of what we say is nutrient sensing pathways also mitochondrial function potentially decreasing your protein intake will enhance biogenesis and efficiency of them of the mitochondria and it causes increased atp production and it causes a reduction of reactive oxygen species, okay? So there is a high protein diet also potentially reduces electron transport and impairs endurance. So, but this data is a little bit variable here because there's also data to say that dietary protein supplements increased mitochondrial respiration. So is that, um, what does that exactly mean? Uh, it's the jury is still out on that part, whether this truly because of this, uh, discordant data would suggest that the full story is not known yet.

Dr. Brent Laartz

 However, we do know at least some of this. Also, metabolic health. This third situation here where decreasing your protein intake causes adipose tissue stimulation, thermogenesis, increased energy expenditure. And this all goes through the FGF21 pathway. That's the fibroblast growth factor 21 pathway. This is a nutrient sensing factor that increases thermogenesis. of white adipose tissue and it regulates lipid homeostasis so and then this lipid homeostasis causes reduced adiposity and it balances your blood glucose and and causes improved insulin sensitivity the opposite of what we thought from all these carnivore diets where people were losing weight because they didn't have carbohydrates and sugars where they, we think that those carbohydrate diets have improved outcome.

Dr. Brent Laartz

 However, these carnivore diets actually are shown to increase mortality, not decrease it, even though there is definitely some weight loss here. Again, the jury is still out on Um, mouse studies, however, some of the metabolic health studies are actually in humans. So, um, let's talk about epigenetic modifications because, um, again here with the branch chain amino acids, um, reduction in intake. We find that DNA methylation and post-translational modifications of the histone tails of the DNA allow organisms to adjust gene expression without altering the underlying DNA. That phosphorylation and methylation, acetylation, all can be used as molecular markers of his cellular aging. And it's been known since.

Dr. Brent Laartz

 1944 1945 the dutch winter of 1944 1945 where they had a starving population because of a severe food restriction if they took those persons and their offspring, those persons were found to have the, that had calorie restriction. It blunted age associated changes in DNA methylation. And then, and that even occurred through generations. Okay. The whole sense here, we know that calorie restriction. improves a whole host of different, all of these pathways to healthy aging, calorie restriction. And, you know, certainly there's more ways to do calorie restriction, but essentially you have to restrict pretty much everything. So if you restrict everything across the board, have a healthy whole food diet and...

Dr. Brent Laartz

 Keep some protein intake, keep some carbohydrate intake, have a healthy balanced diet and couple that with everything else we've talked about the other pillars. So your movement, your exercise, cardiovascular and resistance training and sleep and decreasing your ultra processed foods and then that's potentially a no-brainer as far as aging, longevity, prevention of dementia, a Mediterranean diet, a MIND diet that decreases red meat intake, decreases protein, decreases carbohydrates, decreases simple sugars, decreases ultra- processed foods okay so again here so the last part of cellular senescence and autophagy we already talked about that as far as the autophagy because of decreased mTOR activity but some of these studies also here show that that senescence is also modified.

Dr. Brent Laartz

 And senescent cells, when they are in your body, are these ghost cells. They produce senescence-associated secretory phenotype, producing pro-inflammatory markers. They promote tissue dysfunction, accelerates cellular aging, while the clearance of senescent cells can ameliorate that age-related disease. And this decreased protein intake reduces the accumulation of senescent cells. increases autophagy, and it decreases that cellular senescence-associated secretory phenotype of these so-called ghost cells. And then this leads to potentially all five of these together. Perhaps these are another five pillars of protein restriction and or calorie restriction. It's not just protein restriction, but that seems to be a big part of it. Because again, isoleucine by itself increases mTOR activity. We don't want to mTOR increase activity, okay?

Dr. Brent Laartz

 So healthy aging and longevity, extended health span, increased longevity, delayed age-related decline. decline, enhance vitality, and increase disease resistance. So disease resistance from cardiovascular disease, diabetes, mellitus, and dementia, et cetera. So, all right. So what if you, what if the low protein diet and resistance training is the key? Okay. So The resistance training improves your muscle activity, improves your strength while you are on this low-protein diet. Instead of a high-protein diet and being sedentary, a lot of these studies were of sedentary adults, sedentary older adults, where they showed increased protein needs. What if it's just resistance training you need? So again, I'm not here to tell anyone what to do. This is not advice.

Dr. Brent Laartz

 This is just showing you this data of this, these studies and this review that's really important here. All right. So at a younger age, high protein might be needed for growth. And or if you are dealing with some kind of healing pathology or some other. pathology where you absolutely need higher protein that's something completely different but potentially for older individuals it may not be as simple as what what we're hearing from all of these gym bros who are saying that we should have 1.2 grams per kilogram or or one one gram per pound of body weight. Okay, so fish, beans as a protein source. The sarcopenia studies for increased protein intake have been variable.

Dr. Brent Laartz

 All right, so let's talk about first this other This study, so this is the Dietary Restriction of Isoleucine Increases Healthspan and Lifespan of Genetically Heterogeneous Mice. Okay, so this, let's get to this article here. All right, so, and if I show this one... graphic here of males and females and show the increased lifespan of the mouse with the low and this is this ILE here is isoleucine so this is the low isoleucine diet if I show this one slide this is only like one tenth of the study This study went through a complete run through of the health and metabolic health of these mice in this isoleucine study and isoleucine restriction.

Dr. Brent Laartz

 actually improve the metabolic outcome, the, let's say even liver, uh, outcome and fatty liver outcome. Um, just here, I'm just going to, um, look at energy expenditure increased. Again, we talked about that, right? We talked about. the fact that protein restriction can increase energy expenditure. There was definitely an increase in energy expenditure. There was energy expenditure increased in fat cells. All right, so then it looked at circulating FGF21. increase basically in these mice that were fed this restricted diet. So it kind of suggested that again, that was the pathway to it. Cancer prevalence actually decreased amongst the isoleucine mice uh isoleucine restricted mice i should say um yeah just a whole host i mean if if i were to there were probably

Dr. Brent Laartz

 100 graphics of everything they did in this study it's just a very complete study in these genetically heterogeneous mice which is important for humans right because humans are not um genetically homogeneous like some of these mouse studies are done in in genetically identical mice right so these are genetically heterogeneous so that they could have um so that they didn't have any confounding by being in a statistically identical mouse each one of them okay so um so here let's go and then let's look at here so this is actually looking at again the lifespan of the mouse um if this is the low ile

Dr. Brent Laartz

 diet on the right for males you can see that they lived about let's say it's 1150 median days and though the control mouse was living about 950 days so you can see there it's a 33 increase in the lifespan of the male mouse here uh on the right on the right of the of the graphic, you can see the females was only a 7% decrease increase in lifespan, but it was significant. Okay. So, all right. So this is an interesting article and This was a while back. This was 2023. All right, so then let's look at the other article really quickly. I don't have... All right. So I've stopped sharing there. So, all right.

Dr. Brent Laartz

 The, I don't have any graphics for the third article, but the interesting thing here was just that they took, uh, British twins, and there were 3,300 participants, and they were an age to mean of 72 years. So they were somewhere between, let's say, 65 and 80 years of age. They were all monozygotic. Actually, 45% of them were dizygotic twins, and there were 168 individual lone twins. In other words, not having a comparison. Using optimal protein intake as a reference group. So the reference group, if they had one approximately gram per kilogram per day, that was optimal. and there was no significant association between protein intake and low muscle strength, or between low protein intake and sarcopenia.

Dr. Brent Laartz

 If the person's had a high protein intake greater than 1.3 grams per kilogram per day, that was associated with low muscle mass. and that low protein intake was protective. So an odds ratio of 0.52. So half as likely to have sarcopenia than the high protein intake. Okay, so let's... Think about this, so as to, it's an important study. This was from 2023. It was from the Age and Aging Journal. We'll put the journal articles in the show notes, but there's been a lot of studies showing that potential sarcopenia of either caloric restriction, weight loss, the GLP-1s, and there's been some data to suggest that the sarcopenia of this weight loss can be mitigated by resistance training and that

Dr. Brent Laartz

 of older adults requiring a higher dose of protein to achieve that same response in muscle protein synthesis as younger adults. That certainly has been known, but that's potentially for the same anabolic response, right? So if you're going to build muscle, right? So we're talking about not losing muscle, okay? So, and Certainly there's some guidance here that we need to take into account. And so what could be at play here as far as this goes? And these were measured by DEXA scan. And I think that some of the studies use different. routes to measure the sarcopenia and this uses dexa scan for for information purposes okay so so sarcopenia

Dr. Brent Laartz

 was associated with the high protein intake, but muscle strength in this study was not associated with that high protein intake. Okay, so there was no association there. So what could be at issue here? And they did control for a lot of different variables here. One could argue that there might be a reason why these people were eating a higher amount of protein. Maybe they were told that they needed to eat a higher amount of protein for some reason, okay? And so maybe that's why there was associated with sarcopenia.

SPEAKER_2

 Maybe they were told because of some medical illness or something along those lines.

Dr. Brent Laartz

 There were other things in the study that were associated with sarcopenia also, and we all know that smoking is associated with sarcopenia. And if you have... an older age, that's definitely associated with sarcopenia. So if you were 60 years versus 80 years old, if you're on the bottom of the end versus the upper end, you're definitely going to have more sarcopenia if you are aged. The other thing, Again, that was highly associated with protein per weight in grams per kilogram per day. So the higher that was. So lower sarcopenia was associated with height, education, appetite score, gait speed. which is an association of fitness, perhaps. If your creatinine is lower, you have less sarcopenia. So people with a... higher serum creatinine have sarcopenia.

Dr. Brent Laartz

 All right. So, all right. So they control for all of these variables in this study. So, but one thing they can't control for is potentially what is the reason why they're eating on that high protein diet? Okay. So let's see. All right. So again, here, thanks for joining us on Sunday Science on Go On Pro. I really wanted to get this out there. I really want you guys to look at this article because I think that longevity wise. Higher dietary protein intake is not the way to go for me because overall calorie restriction needs to have overall protein restriction. We need nutrient sensing, but at the same time, you can't be a sedentary adult. and have a low protein intake.

Dr. Brent Laartz

 Because if you're going to be a sedentary adult, you are going to lose muscle. And you're going to lose it more if you have low protein. So if you're going to be a sedentary adult, certainly by all means, listen to your doctor. and hopefully listen to your doctor about the fact that you're sedentary okay um i don't want to be sedentary i don't want to be sedentary because that's going to lead to a less healthy life in the long run more morbidity in the long run so i am espousing calorie restricted whole food and

Dr. Brent Laartz

 calorie restricted protein restricted carbohydrate restricted and whole food mostly plant-based and decreased red meat and obviously then at the same time along with that resistance training cardiovascular training and better sleep and better purpose and better connection, better creativity, and then also decreased ultra processed foods, decreasing the amount of plastics in my life. All five of these pillars, again, really look at this article. I think that You'll be amazed at the way they lay out every single one of the points of these studies and all of the articles they bring into this review that Dr. Lamming has brought in. At some point, I think this is one of the, you know, I don't have guests on my podcast.

Dr. Brent Laartz

 I'm just talking about these studies. myself. I'm not going to really bring in guests yet, but at some point, if I was to bring in a guest, I think this guy would be one of the first guys I would bring in, along with some of the people from the University of Washington and Stanford that are at the foremost forefront of aging research. And I think this is an important one. here. So get this article, review it. I don't care how you need to get to it, but get to it and see the review on protein restriction, because it could change your mind about how you view protein intake. And what the gym bros are telling you, it might change some minds. All right.

Dr. Brent Laartz

 Thank you very much for joining us. I look forward to seeing you guys in the future. Catch us on GoOnPro.com. Catch us on Substack. Catch us on YouTube. Catch us on Spotify, Apple, podcasts. We can see video podcasts. podcast. Obviously, if you're listening to us again, I tell you every time that we're on this podcast, that if you can't see the graphics that I put up, it's because you're on an audio podcast, get to get to a video podcast, check it out. And you can see all of this from the Um, from the article too, they have a, they have their own graphic in here looking at the, um, aging longevity too, but thanks for joining us folks.

Dr. Brent Laartz

 Uh, we'll talk to you soon. We'll see you on the flip side. Thanks.

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