#370 - AMA #76: Peter evaluates longevity drugs, aspirin for CVD, and strategies to improve muscle mass — proven, promising, fuzzy, noise, or nonsense?

View the Show Notes Page for This Episode https://peterattiamd.com/ama76/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama76&utm_content=251027-pod-ama76-podfeed Become a Member to Receive Exclusive Content https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama76&utm_content=251027-pod-ama76-podfeed Sign Up to Receive Peter's Weekly Newsletter https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama76&utm_content=251027-pod-ama76-podfeed In this "Ask Me Anything" (AMA) episode, Peter revisits the "proven, promising, fuzzy, noise, nonsense" scale and applies it to a variety of popular topics. He begins with a refresher on what each category represents before classifying a range of interventions based on the strength of their supporting evidence. The conversation spans three main areas: drugs for geroprotection (including GLP-1 receptor agonists, SGLT2 inhibitors, methylene blue, and telomere-lengthening supplements), the use of low-dose aspirin for cardiovascular disease prevention, and strategies to improve muscle mass through optimal protein intake and follistatin gene therapy. This episode provides a clear, evidence-based overview for listeners seeking to understand where these popular health and longevity interventions stand on the spectrum of scientific credibility. If you're not a subscriber and are listening on a podcast player, you'll only be able to hear a preview of the AMA. If you're a subscriber, you can now listen to this full episode on your private RSS feed https://peterattiamd.com/members/private-podcast-feed/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama76&utm_content=251027-pod-ama76-podfeedor our website at the AMA #76 show notes page http://peterattiamd.com/ama75/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama76&utm_content=251027-pod-ama76-podfeed. If you are not a subscriber, you can learn more about the subscriber benefits here https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=251027-pod-ama75&utm_content=251027-pod-ama75-podfeed. We discuss: A scale for evaluating scientific claims: proven, promising, fuzzy, noise, or nonsense [1:30]; Strong convictions, loosely held: the mindset that separates great scientists from the rest [7:30]; GLP-1 receptor agonists: are there benefits beyond improving metabolic health and promoting weight loss? [12:45]; GLP-1 drugs and the brain: exploring the potential cognitive benefits [18:45]; GLP-1 drugs and lifespan: examining the evidence for potential geroprotective effects [23:00]; Rapamycin and geroprotection: why it remains in the "promising" category [25:45]; SGLT2 inhibitors and their potential geroprotective effect [27:30]; Methylene blue: examining the evidence of an anti-aging effect [34:45]; Methylene blue's potential neuroprotective effects: limited and inconsistent evidence in humans, and the challenges of dosing and safety [41:15]; Telomeres: what they are, how they relate to aging, and why telomere-lengthening supplements lack credible scientific evidence [43:45]; Does the idea of targeting telomere length to extend lifespan have scientific merit? [50:15]; Low-dose aspirin for cardiovascular disease prevention: weighing its clot-prevention benefits against bleeding risks across different populations [55:00]; Rethinking the protein RDA: why most people need twice the recommended amount for muscle health [1:00:45]; Debunking the protein–cancer myth: why higher protein intake doesn't promote tumor growth [1:06:15]; The biology of follistatin and myostatin, and why follistatin gene therapy has become an emerging topic of interest for muscle growth [1:13:15]; Follistatin gene therapy for muscle growth: state of the evidence in animals and humans, and the technical challenges and regulatory barriers [1:17:00]; Why injectable follistatin is theoretically possible but impractical for real-world use [1:23:15]; and More. Connect With Peter on Twitter https://twitter.com/PeterAttiaMD, Instagram https://www.instagram.com/peterattiamd/, Facebook https://www.facebook.com/peterattiamd/ and YouTube https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:10Dr. Peter Attia?

  Hey everyone, welcome to a sneak peek Ask Me Anything, or AMA, episode of the Drive Podcast. I'm your host, Peter Attia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peterattiamd.com/subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything AMA, episode number 76. In today's AMA, we revisit the Proving, Promising, Fuzzy, Noise, Nonsense Scale, and apply it to a variety of commonly

• 0:53Dr. Peter Attia?

  inquired about and hot-button topics. We start with a quick reset on what each bucket means, and define them, of course, and then we walk through every topic where we're going to land on. So the goal of this episode is that if you're coming to this topic without any previous background, or you just want the TLDR, this is the place for you. We group the topics by the intended outcome. And there are three categories today. Drugs for Gero Protection, where we cover GLP-1 agonists, SGLT2 inhibitors, methylene blue, and telomere lengthening supplements. Talk about low-dose aspirin for CVD prevention. And then we look at interventions to improve muscle mass, talking specifically about protein, but also

• 1:35Dr. Peter Attia?

  Follistatin gene therapy. If you're a subscriber and want to watch the full video of this podcast, you can find it on the show notes page. And if you're not a subscriber, you can watch the sneak peek of this video on our YouTube page. So without further delay, I hope you enjoy AMA 76.

• 1:59Speaker 01

  Peter, Artie, doctor, podcaster, author, speaker, bad chess player. How are you doing today?

• 2:09Dr. Peter Attia?

  Hey, hey, hey, hey, hey, hey, hey. You could say shepherd in there. You don't have to, you don't have to take sheep shots.

• 2:15Speaker 01

  Shepherd of diabetic sheep, race car driver. Anything else missing?

• 2:21Dr. Peter Attia?

  Oh, that's good.

• 2:23Speaker 01

  That's good. All right. I just didn't want to forget the diabetic sheep out there. That's true. That's true. How's the day going today?

• 2:30Dr. Peter Attia?

  Started out good, then took a little dip with the follow-up chess match. But there's a recurring theme here that you, I know you just love picking this scab.

• 2:39Speaker 01

  Well, I just, sometimes you think about feats like Tom Brady, right? Like what he went through.

• 2:46Dr. Peter Attia?

  Greatest of all time. Right.

• 2:47Speaker 01

  Yeah. People who come back from injuries. Damar Hamlin, like almost died, came back and played. I mean, like you getting second in a four-person in-house chess tournament with two children has to be up there, right?

• 3:03Dr. Peter Attia?

  Listen,

• 3:07Dr. Peter Attia?

  we all started playing at the same time.

• 3:09Speaker 01

  Gopcha just won the tour again. Went through two in a row. Grueling. Not as mentally tough as what you went through, though, a month ago.

• 3:19Dr. Peter Attia?

  I would argue what I go through on the daily, trying to just make sure I don't get beat by an eight-year-old in chess is at least on par mentally with some of the feats you're talking about.

• 3:32Speaker 01

  We need to have Tom on the podcast and you should ask him about it. Which one was harder? All those Super Bowls.

• 3:38Dr. Peter Attia?

  Is it harder to be down 28 to three, having thrown a pick six in the Super Bowl? Or succumbing to an eight-year-old's gambit? Which is tougher?

• 3:52Speaker 01

  To be fair, there is a real chance the eight-year-old might have talked more trash than what was going on in the Super Bowl, which says something. Yep.

• 4:02Speaker 01

  All right. So today's AMA, not about chess, gonna be a little different. So what we're gonna do is cover a variety of topics, looking at it through a certain lens, which is, we are gonna take concepts and things that we've talked about before, some new things that we haven't talked about before, that we get asked about a lot. And instead of going super deep in them, we're gonna kind of summarize them into how you think about them. And we're gonna do it into five different buckets. And those buckets are proven, promising, fuzzy, noise, nonsense. People who have listened for a bit will remember this. We did this in episode 300 of the podcast, which was back in May 2024. So it's been a little bit, but people really liked it because it allowed us to cover

• 4:47Speaker 01

  a variety of topics, it allowed us to summarize them, and it allowed us to kind of look at them in an apples to apples comparison with what we know about them and how people should be thinking about it. So in today's episode, we are gonna look at some GRO protective drugs like GLP-1s, things like Ozempic, SGLT2 inhibitors, both of which we talked about before. We're gonna look at methylene blue and telomere lengthening supplements. Those are kind of newer. We're gonna look at what we know about low dose aspirin and cardiovascular disease prevention. And then we're gonna look at interventions that can help improve muscle mass, things like protein Follistatin gene therapy, et cetera. Hopefully, a good variety of things for people, hopefully, kind of a way to go through it

• 5:33Speaker 01

  where people can kind of look, get clear, clean takeaways. With that said, anything you want to add before we get rolling?

• 5:42Dr. Peter Attia?

  No, but maybe I will just remind people, or for folks who are new to the program, what these categories mean. So you mentioned five, and we're starting from the most promising or the closest to quote unquote, truth, which we're calling proven, although I put proven in quotes because technically, nothing in biology is proven, right? It's not like mathematics where you prove something and write Q E D at the end and never have to think. Think about it again. So proven would be as close to well-established claim as you're going to find. The implication for us, of course, is you've got lots of high-quality, consistent data. The category beneath that would be promising. This is a category where

• 6:23Dr. Peter Attia?

  the claims look good, there are data to support it, but maybe we're still waiting on replication, or maybe most of the data are moving in one direction, but not all of it, or something like that. Category beneath that we call fuzzy, and this means there are some data around the claim, but they are really inconsistent and incomplete. So overall, you would say the data quality here is not that great, but there's probably a signal. Beneath that, we have noise. So here, we have something where there are just frankly, no real meaningful results. So noise is something that, it's not that I'm saying you shouldn't pay attention to it,

• 7:04Dr. Peter Attia?

  but you clearly don't want to be distracted by it, and it's best to wait and see if noise declares itself by going up to fuzzy with the presence of some data as it works its way up the chain, or whether data actually emerge that put it in the final category, which is actual nonsense. So again, nonsense means we actually have data, and the data refute the claim being made. So as far as we can tell, this is as close to disproven as you'll be. So again, those are the five categories. Just kind of keep that in mind as we apply our judgments to these things. And keep in mind as well that these are fluid. Things can move up and down these chains in the presence of new information.

• 7:45Speaker 01

  Yeah, and I think I always like to anchor people to this. And so we've talked about it before, but I do think it's helpful, which is, sometimes I think in today's day and age, where people are very confident in their opinions, and usually kind of stick to them, you see it a lot in nutrition, where it's like you just get in a camp and you stay with it. Do you just want to talk a little bit about your idea of strong convictions loosely held and why you think it might be counterintuitive when people change mind and something goes from proven to promising or goes up and down, but just how you think about when new data comes, you just have to be unemotional to it and just take science for science?

• 8:26Dr. Peter Attia?

  Yeah, look, I think first and foremost, that's an attribute of great scientists. So if you look at what separates good scientists from great scientists, that would probably be one of the characteristics. A great scientist is not married to being right, they're married to knowing what is right and they're going to go wherever the data take them. But honestly, the first time I heard that expression, to have strong convictions loosely held, was actually from a friend of mine who at the time was running a hedge fund, he's since retired. But he said, look, that's the key to being a good investor is you have to have strong convictions because you're going to be putting a lot of capital at risk, but those convictions have to be loosely held.

• 9:06Dr. Peter Attia?

  So the moment that data emerge that change your thesis for investment, you have to be flexible enough to move as opposed to double down. And the reason I think that this is such an important part of investing is in science, if you're wrong, the price is not that severe. In fact, without calling out or embarrassing anybody, there are lots of people who have taken positions on things that are just so patently incorrect 20 and 25 years later, and yet they just can't let go of their baby. They can't kill their baby. And so frankly, they just make fools out of themselves, continuing to cling to ridiculous beliefs, but there's actually no real price they're paying for that, other than within the scientific community they're laughed at.

• 9:51Dr. Peter Attia?

  But you can't be an investor, you can't be a money manager with that type of mentality because you'll be out of business. And so in the final analysis, the dollars talk louder than anything else. And if you continue to double down on horrible positions, you will lose the money of your LPs and ultimately you will be broke. So I think that's sort of why it's a great idea to be thinking about. Through the lens of how an investor functions. And so I think we just have to all try to do that. It's hard. It's hard to kill your babies. But that was the expression. Those were the exact words that were used when I first showed up in the lab and first started doing experiments and first started getting my data and trying to put hypotheses together and make sense of what I was seeing.

• 10:33Dr. Peter Attia?

  You can have the most beautiful, beautiful hypothesis ever, and it can be categorically slayed by ugly facts. And that's paraphrasing a quote. God, I don't remember who actually said that quote, but it's a sort of famous quote in science.

• 10:47Speaker 01

  Yeah, I think it's just good for people to kind of anchor that, too. So, starting off, if you had to put the following statement into one of those categories, where would it be? Which is, "The next in-house tournament, Peter Attia takes first place."

• 11:03Dr. Peter Attia?

  Listen, I believe I have the potential to beat my young boys in chess, provided I don't get distracted by the smack talk. In my defense today, by the way, I know you don't play chess, but just so you understand, I promoted a pawn to a second queen on the 25th move. Do you understand what an advantage I had in this game today? I've got two queens on the board and I was ahead on material before that promotion. This was a bloodbath. And then he starts yapping so much and makes what looks like an idiotic blunder, exposing his rook to my newest queen. So, of course, I take the free rook.

• 11:48Dr. Peter Attia?

  But I was so dumb when I did it that I didn't notice that he moved his bishop out of the way, what looked like a blunder, so he sacrificed his rook, to put his bishop in a way to basically create what's called a battery against my king. And the next move, he checkmated me. So you could say, okay, I got beat. Yes, I did. But part of it is I was distracted by how much he was yapping. So all I really need to do to up my game is just not get distracted. I think I have a good chance to win the next in-house tournament.

• 12:20Speaker 01

  I do love your kryptonite is second graders who talk trash, whether it's chess, whether it was the kid who was just giving you tons of crap for drinking a diet soda at the school lunch, wherever it is.

• 12:36Dr. Peter Attia?

  There could literally be a sitcom of me going through my life, just getting broken down by eight-year-olds, just getting put in my place.

• 12:47Speaker 01

  It's like the Seinfeld episode where the shrimp comment, a day later, he rethinks of what the comeback should have been. I just anticipate that's you, like going to sleep at night, being like, oh, man, when Ari said this, if I would have responded with this, I would have got him so bad. Next time, next time, I'm not going to let that eight-year-old talk that trash to me.

• 13:10Dr. Peter Attia?

  So good.

• 13:11Speaker 01

  Well, real thing we're going to start with, geoprotective drugs. So there's a lot of questions about drugs that have metabolic health effects and what that means for anti-aging. So instead of just looking at this improves metabolic health, is there something special about those that can also be anti-aging? And on a side note, just it'll be good to explain what geoprotective drugs are. We've done it before, but I think it's good for a quick reminder. But outside of that, the biggest drug that is in the news all day, every day, GLP-1s, Ozempic, trisepotide, Wegovy, you name it, everyone's heard of it. We've done a lot about that. So the question is, do we know anything if they have a unique

• 13:57Speaker 01

  anti-aging effect that actually improves lifespan outside of the metabolic health effects they have?

• 14:05Dr. Peter Attia?

  Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive, member-only content and benefits above and beyond what is available for free. So if you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode.

• 14:48Dr. Peter Attia?

  And the word on the street is, nobody's show notes rival ours. Second, monthly Ask Me Anything or AMA episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused on a single topic and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access to the show notes for these episodes, of course. Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you with access to every episode, including AMAs,

• 15:33Dr. Peter Attia?

  sans the spiel you're listening to now, and in your regular podcast feed. Fifth, the Qualies, an additional, member-only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally, other benefits that are added along the way. If you want to learn more and access these member-only benefits, you can head over to peterattiamd.com/subscribe.

• 16:05Dr. Peter Attia?

  You can also find me on YouTube, Instagram, and Twitter, all with the handle Peter Attia MD. You can also leave us a review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any

• 16:50Dr. Peter Attia?

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