The biology of aging, rapamycin, and other interventions that target the aging process 28,451 views Sep 13, 2021

175 - The biology of aging, rapamycin, and other interventions that target the aging process 28,451 viewsSep 13, 2021 725 DISLIKE SHARE DOWNLOAD CLIP SAVE Peter Attia MD 131K subscribers Matt Kaeberlein is globally recognized for his research on the biology of aging and is a previous guest on The Drive. In this episode, Matt defines aging, the relationship between aging, chronic inflammation, and the immune system, and talks extensively about the most exciting molecules for extending lifespan. He discusses the current state of the literature of testing rapamycin (and rapalogs) in animals and humans, including Matt’s Dog Aging Project, and provides insights into how we can improve future trials by conceptualizing risk, choosing better endpoints, and working with regulators to approve such trials. He also examines the connection between aging and periodontal disease, biomarkers of aging, and epigenetic clocks. Finally, they explore some of the biological pathways involved in aging, including mTOR and its complexes, sirtuins, NAD, and NAD precursors. We discuss: 00:00:00 - intro 00:00:10 - The various definitions of aging 00:14:08 - The relationship between disease and the biology of aging 00:20:55 - Potential for lifespan extension when targeting diseases compared to targeting biological aging 00:31:30 - Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules 00:38:56 - Human studies using rapalogs for enhanced immune function 00:51:22 - The role of inflammation in functional declines and diseases of aging 00:56:56 - Study showing rapalogs may improve the immune response to a vaccine 01:02:26 - Roadblocks to studying gero-protective molecules in humans 01:14:44 - Potential benefits of rapamycin for age-related diseases—periodontal, reproductive function, and more 01:24:40 - Debating the ideal length and frequency of rapamycin treatment for various indications like inflammation and longevity 01:32:38 - Biomarkers of aging and epigenetic clocks 01:41:05 - Prospects of a test that could calculate biological age 01:47:28 - The Dog Aging Project testing rapamycin in pet dogs 02:05:00 - The role of the mTOR complexes 02:16:53 - mTor inhibitor called Torin2, mitochondrial disease and other potential pathways 02:27:24 - Catalytic inhibitors, sirtuins, and NAD 02:36:47 - NAD precursors: help or hype? Show notes page: https://peterattiamd.com/mattkaeberle... -------- About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Chapters intro 0:00 The various definitions of aging 0:10 The relationship between disease and the biology of aging 14:08 Potential for lifespan extension when targeting diseases compared to targeting biological aging 20:55 Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules 31:30 Human studies using rapalogs for enhanced immune function 38:56 75 Comments rongmaw lin Add a comment... Peter Attia MD Pinned by Peter Attia MD Peter Attia MD 8 months ago In this episode, we discuss: 00:00:00 - intro 00:00:10 - The various definitions of aging 00:14:08 - The relationship between disease and the biology of aging 00:20:55 - Potential for lifespan extension when targeting diseases compared to targeting biological aging 00:31:30 - Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules 00:38:56 - Human studies using rapalogs for enhanced immune function 00:51:22 - The role of inflammation in functional declines and diseases of aging 00:56:56 - Study showing rapalogs may improve the immune response to a vaccine 01:02:26 - Roadblocks to studying gero-protective molecules in humans 01:14:44 - Potential benefits of rapamycin for age-related diseases—periodontal, reproductive function, and more 01:24:40 - Debating the ideal length and frequency of rapamycin treatment for various indications like inflammation and longevity 01:32:38 - Biomarkers of aging and epigenetic clocks 01:41:05 - Prospects of a test that could calculate biological age 01:47:28 - The Dog Aging Project testing rapamycin in pet dogs 02:05:00 - The role of the mTOR complexes 02:16:53 - mTor inhibitor called Torin2, mitochondrial disease and other potential pathways 02:27:24 - Catalytic inhibitors, sirtuins, and NAD 02:36:47 - NAD precursors: help or hype? 18 David David 8 months ago The Drive remains amongst the very best longevity podcasts, and this was one of the best episodes. 13 Paula Samec Paula Samec 4 months ago I ( a female, then 74 years old ) had two infections within three weeks’ period in spring of 2020, probably the second could have been COVID since it was pretty severe with very high fever but I put out fever within four days, the second one after sweating profusely and not eating, just drinking and resting but not taking any medicine just some antimicrobial ointment for the nostrils and throat. I was completely well after a week! 2 Scott K Scott K 8 months ago By far one of your best pods. Aside from the wellspring of interesting info that is Matt K, your skills as an interviewer are dramatically improved, compared to the earlier pods. Namely, you seem to be honing in on the ideal balance between being inquisitive and conversational, on the one hand, vs being patient and letting the guest elaborate, on the other. This podcast was also the ideal ratio of depth and breadth. Seems like you're really getting the knack of knowing when you'v reached sufficient depth that it's time to segue into the next topic. Bravo sir. 7 Alexis Espinosa Alexis Espinosa 8 months ago I'm still very surprised why Prof. Valter Longo has not been in the show yet! Please invite him! I imagine your chat with him to be fascinating! Thanks Peter! Amazing episode! 11 Stephen Hazel Stephen Hazel 8 months ago (edited) thanks for sharing this whole episode with even us freeloaders :) much appreciated !! This is probably the most valuable info I've received in my entire life :))) 5 Anthony Lawrence Anthony Lawrence 8 months ago The context, timing and dose are interesting and very important. Naltrexone is another very good example. In low dosage (up to 4.5mg) the effects are massively different, as well as the timing in many cases. 2 Craig Harding Craig Harding 8 months ago Glad Dr A talked about his own self-regimen - at the 38 min mark. 20 Dave M Dave M 8 months ago (edited) Great podcast. Great to hear what they do know, what they don't know, self experimentation, and speculation. Also nice to see Peter mention senolytics and voice an opinion on epigentic clocks. 1 Влад Третьяков Влад Третьяков 8 months ago Protein and carbs stimulate mTor via different pathways. Does it mean it's beneficial to switch to fat metabolism(low carb, keto) to receive the benefits rapamycin gives? 5 Judith Montel Judith Montel 8 months ago The studies showing rapalogs' improving immune response to vaccines in older adults is particularly of interest right now as I'm following the very detailed data on the Israeli Ministry of Health's data dashboard on covid. They show that while people 60 or over are a relatively small fraction of those infected, they constitute the vast majority of those seriously ill and this includes people vaccinated fully and even with a booster. At this point in time, finding any way to improve immune response in older adults could have a significant impact on a number of issues: the rates at which older adults become seriously ill and die, the pressure on the health care system, and through this, alleviate the overall pressure on society that comes with dealing with this disease. G.C.W G.C.W 6 months ago Thank you. Another great show. Jason Haxton Jason Haxton 1 month ago Thanks Peter and Matt. I have listened completely thru this podcast while traveling 4-times. Seriously! I never get tired of it. Such a nice balance of information, research and personal input. You really understand and can explain this difficult subject matter. I keep picking up a bit more (this covers such a breadth of material on aging). FYI - I am going on 2-years of rapamycin use once a week 6mg - precribed by my personal physician and blood monitored every 3 months. He and I can't believe the amazing results in pushing back on the biological age in all my organs. I will be 64 years young in 1 week. But, feeling more like my TRuMe epegentic 50 year biological age reading. BTW - Matt's comment there is no such thing as a healthy 65 year old. Ouch. I guess I have one more year of health. Hahaha. Proof of Rapa effectiveness! Jason Anthony Lawrence Anthony Lawrence 8 months ago The Glycome is a very interesting test of biological age. GlycanAge run by Prof Gordon Lauc in Zagreb. 1 mark veen mark veen 8 months ago (edited) People always talk about rapamycin, metformin, resveratrol and NMN in a slower aging sense. But if you dont even know the exact dose and are flying blind. What makes you think to high doses cannot result in accelerated aging? 2 jods jods 8 months ago Since both of you take Rapamycin, curious about your oral health now. Just basic answer - is it SAME, BETTER, WORSE? 8 Mark Armani Mark Armani 8 months ago (edited) Wish they'd have expounded upon the dosing in the dog trial. .15mg/kg = 11.25mg /week for a 75kg human. With Peter/most taking 6-8mg/week, this is much higher. Why? He talks abt being conservative for sides in dogs, but this is a high dose. With mice trials showing males do better on higher dose, I'm wondering if 6-8m is too low for maximum efficacy? 2 Julie Williams Voiceover Momentum Julie Williams Voiceover Momentum 3 months ago I had a severe toxic reaction to Metformin. And it depletes CoQ10 & B12 TheShumoby TheShumoby 8 months ago Longevity certainly have some genetic aspects to it. All of my grandparents lived over 96+ years. My maternal great grandfather lived to be 106. I checked my genetic SNPs I have most of the longevity markers. 4 Mick Mack Mick Mack 7 months ago (edited) ... hey one more thing. I think nr and nmn are great molecules, im convinced it works, and most important its SAFE!!! Its easy to jump on the rapamycine band wagon but its hard to find out later that the wagon has got no breaks. I personally only take niacin and its fantastic, from my own experience, i perform much better..... its great to hear about rapamycine but please not on the costs of the benefits of other safe remedies, at least for the time until rapamycine has been searched properly.... and by the way, no one claimed that nmn etc could extend lifespan Eris D Eris D 8 months ago Where does Matt and Peter source their Rapamycin from? Looking for the highest quality. 4 Aloe Vera Aloe Vera 3 months ago (edited) In response to the Understanding of aging vis a vis the Treatment of it in health or disease states — which mirrors the epistemic opacity in many fields — I’ll drop the title to one of my favorite papers by Nassim Taleb: “**Understanding is a Poor Substitute for Convexity (Antifragility**)“. The heuristic is that when you detect acceleration of harm (fragility) then it’s safe to avoid something instead of over intervening (iatrogenics). Like the health-seeker avoiding sugar and starchy carbohydrate instead of waiting for a miracle drug to fix aging in health and disease states. You may not understand why it works but you can detect the acceleration of harm by adding those things back in. So you eliminate fragility. William Chan William Chan 8 months ago (edited) Man, if I were rich enough, I would fund that periodontal study yesterday... Ben Nguyen Ben Nguyen 8 months ago Regarding the 51m mark, on how the immune system malfunctions with age, not so much that it's weak.. how do you measure chronic-sterile inflammation.. P16, P21, markers of senescence? And is it possible that an immune system that responds incorrectly, may lead to the myriad of autoimmune disorders, YET, may be better at warding off cancer? Regarding the known side-effect with Rapamycin (mouth-sores), any thoughts on Nir Barzilai's Aging paper, "Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults", where he says only muscle mass is negatively affected, not strength! "The function of the muscle didn’t change. So if they have less muscle, and the function of the muscle didn’t change, it means that for a gram of muscle, the muscle was better. So I looked at it and took the muscle from those two trials because they had muscle biopsies, and we did a transcriptome. And we basically saw that all the work to get hypertrophy, you have to activate mTOR. And remember when you activate mTOR, it’s not good for aging. So the muscle growth was associated with mTOR, which Metformin blunted, because that’s part of what Metformin does. On the other hand, people on Metformin had a transcript that was a protective transcript for aging with genes for autophagy, against inflammation, and some other things. So there was a trade off. And for me, I’m exercising and I’m on Metformin, for me it’s not that important to bulge my muscles. For me, it’s more about aging. So if you want to show muscles, don’t take Metformin. But I think Metformin protects your muscle from the aging effects. And so if I were you, I would say do it together. And the question of timing, it depends. I’m on extended release Metformin. So it’s not that timing would have a huge effect. And I’m also exercising sometimes in the morning, sometimes in the evening." Would love to hear Keith Baar take on whether PPAR gamma/delta signaling is affected. And where does strength come from, if it's independent of muscle size? For example, in Blood-Flow-Restriction (BFR) weight-training, ex. GoBstrong , KAATSU, would seem to fool the body to react as if heavy weights are being used.. yet without actual heavy tendon-loading, would strength and/or muscle size increase or neither? Obi z Obi z 8 months ago Why don't start a clinical trial on Rapamycin in people, with periodic testing of GrimAge (the best predictor of time-to-death)? 1 Lynn Williams Lynn Williams 2 months ago Can ketone measurement be a bio marker for Autophagy? Mick Mack Mick Mack 7 months ago (edited) .... hmmm a lot of praising of Rapamycin, however the risks are still high. Who ever wants to heal a frozen shoulder, just go Keto for 4-8 weeks, and inflammation will b gone, and for anti aging and reducing mTor, just fasting and plant based diet reduced in protein (for times when not on keto). Should b safe and cheap and legal. a a a a 8 months ago Great interviewee 1 Tom Cullen Tom Cullen 8 months ago Can't find the link to the 2009 UMich paper where older mice on rapamycin had their immune system restored to that of young mice? Dandy Dandy 8 months ago (edited) You say we can't measure autophagy, but aren't there a bunch of proteins used to measure autophagy flux? How are they not biomarkers of autophagy? What am I missing? I was talking to a guy researching mtor and muscle breakdown and much of his research revolves around measuring autophagy. 1 Mistralis Hoffmann Mistralis Hoffmann 8 months ago All you need is an expensive mic to sound expertly. Double A Double A 8 months ago Matt is far to conservative to be in medicine. The would never be any new drugs developed if he was in charge. Eugene Lynch Eugene Lynch 8 months ago who is downvoting? Must be Sinclair and his disciples. 4 Asia Expat Asia Expat 8 months ago Is it wise for me to go and get some rapomycin and take 1mg per week for 3 months. Im 62 and I think in good health 3 matkaGrogan matkaGrogan 8 months ago Ok, so where can I buy rapamycin from? 5 Annoying Mouse Annoying Mouse 8 months ago How soon can we start seeing rejuvenation centers instead of hospitals? 1 preetham shivanna preetham shivanna 6 months ago Amazing violplayer violplayer 8 months ago Enough chit-chat. Just give me a pill now. 5 Emanuel Goldstein Emanuel Goldstein 8 months ago Have you released your book for mental consumption? I am ready to feast. I do not see any hits on Amazon. Peace, health and blessings... Beki Thomson Beki Thomson 2 weeks ago NMN questions are prevalent because we don't need an Rx. Don't you think? Daniel Rodgers Daniel Rodgers 8 months ago So you had inflammation in your shoulder that went away after 8 weeks. And you body couldn't have healed itself in 8 weeks, so it must have been rapamycin. Silly. My take away from this is. Poor studies, poor science, poor data. Silly. If you're going to serious with this subject you really need to get people who understand data involved. Your standards for data are just wrong -to put in nicely. You don't even have baselines and you speak as if you have real data. Come on. 1 Bones Bones 8 months ago NAD!!