Peter Attia MD , 204 - Centenarians, metformin, and longevity | Nir Barzilai, M.D. 70,733 views Apr 25, 2022,

Insights from genetic studies of centenarians and twins 204 - Centenarians, metformin, and longevity | Nir Barzilai, M.D. 70,733 viewsApr 25, 2022 Peter Attia MD 129K subscribers View episode show notes here: https://bit.ly/36CzHME Become a member to receive exclusive content: https://bit.ly/3k03Sk6 Sign up to receive Peter's email newsletter: https://bit.ly/390bX5U Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent. We discuss: 0:00:00 - Intro 0:00:08 - Insights from genetic studies of centenarians and twins 0:11:13 - Genes with protective variants that aid longevity 0:22:23 - The relationship between growth hormone and IGF-1 0:35:37 - Use of growth hormone as a longevity tool 0:44:29 - Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP 0:50:04 - The correlation between high TSH and longevity 0:56:30 - Important pathways for longevity 1:04:38 - Insights from centenarian studies, nature vs. nurture, and more 1:14:56 - The contraction of morbidity that comes with improved healthspan 1:20:56 - Defining healthspan 1:26:14 - Unique perspectives and positive attitudes of centenarians 1:33:32 - Lessons to take away from centenarians 1:38:48 - Metformin overview: history, studies, and potential for gero-protection 1:50:07 - The TAME trial (Targeting Aging with Metformin) 1:59:29 - The challenge of studying metformin in animals models 2:07:27 - How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics 2:14:54 - The search for biomarkers to identify who can benefit from treatment 2:26:29 - The impact of metformin on exercise, and finding the right indication for the use of metformin 2:39:36 - Are NAD precursors geroprotective? -------- 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 40 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://bit.ly/3EIgCWa 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 Insights from genetic studies of centenarians and twins 0:08 Genes with protective variants that aid longevity 11:13 The relationship between growth hormone and IGF-1 22:23 Use of growth hormone as a longevity tool 35:37 Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP 44:29 174 Comments rongmaw lin Add a comment... Peter Attia MD Pinned by Peter Attia MD Peter Attia MD 4 weeks ago In this episode, we discuss: 0:00:00 - Intro 0:00:08 - Insights from genetic studies of centenarians and twins 0:11:13 - Genes with protective variants that aid longevity 0:22:23 - The relationship between growth hormone and IGF-1 0:35:37 - Use of growth hormone as a longevity tool 0:44:29 - Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP 0:50:04 - The correlation between high TSH and longevity 0:56:30 - Important pathways for longevity 1:04:38 - Insights from centenarian studies, nature vs. nurture, and more 1:14:56 - The contraction of morbidity that comes with improved healthspan 1:20:56 - Defining healthspan 1:26:14 - Unique perspectives and positive attitudes of centenarians 1:33:32 - Lessons to take away from centenarians 1:38:48 - Metformin overview: history, studies, and potential for gero-protection 1:50:07 - The TAME trial (Targeting Aging with Metformin) 1:59:29 - The challenge of studying metformin in animals models 2:07:27 - How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics 2:14:54 - The search for biomarkers to identify who can benefit from treatment 2:26:29 - The impact of metformin on exercise, and finding the right indication for the use of metformin 2:39:36 - Are NAD precursors geroprotective? 19 coronadentalarts coronadentalarts 3 weeks ago Peter , Thank you so much for kicking "educational podcasts" in the balls and showing them the path forward to what the laymen like myself are craving . Long format educational podcasts done right are cocaine for the new kind of learning addicts like myself . Im 54 years old and just beginning to appreciate the information i choose to gather equals a better me . I love the variety of great guests and most importantly how you steer the conversations with your questions , which i believe is what makes these kind of high end podcasts so informative . Granted , I am just a regular guy and constantly have to rewind these talks to try and keep up and absorb these kinds of talks and most of the time I find myself lost in trying to track the scent trail of understanding . I wish that my brain could have a more sponging attitude with your podcasts but i am grateful what i can retain and that you are taking my health understanding to a higher level . Cheers to you for your free to all educational services you have provided and carry on with . 22 Dolores Geyer Dolores Geyer 3 weeks ago Great interview. You are both comfortable having a very interesting conversation. I would love to be in these aging studies. I am 80 years old, in good health, look younger than my years. My Dad lived to 93, died from a fall. Mother died from lung cancer at 68, was a heavy smoker. Why aren’t these studies looking at someone like me? 14 simon mojarad simon mojarad 4 weeks ago I love it and it’s refreshing, Peter for the first time started challenging his guest when they refer to flawed studies. 8 Jamiselle Palacios Jamiselle Palacios 3 weeks ago I am new to your podcast, very interesting subjects and totally new concepts for me. Grandma lived to 95 but my mom died at 64. I am in my 40’s with rapidly hormone changes and not to mentioned had gray hair since my 20’s. Would like to know more about visible aging components and their impact to longevity. 5 tim mulder tim mulder 3 weeks ago Like I've said before and I would like to say it again. In order to challenge yourself in the pursuit of physical fitness you need to do something that you enjoy. Improving the quality of your life not necessarily prolonging your life needs to be the primary motivation. One of the greatest benefits of regular vigorous exercise is you gain the strength to do the things that you want to do. I mean just a normal everyday activities are one thing but to do things like going for a hike bowling on a bowling league or even playing ice hockey again after the age of 60. One of the great lies that we've heard over and over all of our lives is your too old to do this and you're too old to do that. But we all need to start somewhere. In my own experience after retiring early at 62 is I decided to start rollerblading and ice skating. Then I began to start in calisthenics and then from there I went into high intensity interval training. Now I play hockey 3 to 4 times a week I play roller hockey ice hockey and street hockey just day before yesterday I had three on three hockey at the local inline roller rink against teenage boys and Young 20-year-olds. I play twice a week at the local ice rink scrimmage hockey against men half my age. But I said all that just to say this that in order to enjoy what you are doing you need to get better at it and so that became a motivation not so much to be better than the other guy but to be the very best that I can be!! 10 Nils from Alaska Nils from Alaska 1 month ago 1) Interesting podcast; thanks for posting. 2) Genes clearly play a role in longevity. But our lifestyles... what we eat, how much we exercise... can influence the expression of our genes. 10 Red Bull Red Bull 4 weeks ago Thanks Dr. Attia! I’m 54 year old male. Last 2 years; 500 mg metformin X2 daily. 200 mg Test Cyp per week. I train almost every day. I’ve put on muscle, lost fat. Now on peptides for more GH release and I’m visibly turning the clock back no matter which clock you use. My experience with metformin has been great! 18 Kevin Gilbert Kevin Gilbert 4 weeks ago Great interview Peter! Good timing just read Nir's book "Age Later". Good read. Looking forward to further research data from TAME. On a side note, I hope I fall somewhere between a patient and "just" a social media follower! LOL! 2 ChillerHR ChillerHR 4 weeks ago (edited) it would bi nice to know, if one wants to experiment a little, what to check prior to taking Metformin for a spin, and how often and what to check during taking it (in terms of possible negative effects I mean), how much to take and how often, and what type of symptoms or effects to be mindful about while on a drug…that would be nice 8 John Egan John Egan 4 weeks ago Has any research been done concerning people with accelerated aging and comparing their genomes and gene expression with the centenarians?I once had a Dental patient with precocious puberty and her condition seemed to suggest accelerated aging and reduced life expectancy. 3 Bill C Thompson - Live Healthy, Finish Strong Bill C Thompson - Live Healthy, Finish Strong 8 days ago I personally have no interest in living to 100, BUT strongly desire to be as healthy as possible until I die at 80-85. Reducing carbohydrates to a minimum and some intermittent fasting has transformed my health. I started this at age 62. I turn 66 next month. I lost a lot of weight, came off ALL medications (2 for hypertension), reduced my HbA1c from 9.9 to 4.9 (without medication). I was also able to give up my CPAP for sleep apnea. 11 Cheryl R Leigh Cheryl R Leigh 4 weeks ago Timestamp from Dr. Attia's Description Box: 0:00:00 - Intro 0:00:08 - Insights from genetic studies of centenarians and twins 0:11:13 - Genes with protective variants that aid longevity 0:22:23 - The relationship between growth hormone and IGF-1 0:35:37 - Use of growth hormone as a longevity tool 0:44:29 - Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP 0:50:04 - The correlation between high TSH and longevity 0:56:30 - Important pathways for longevity 1:04:38 - Insights from centenarian studies, nature vs. nurture, and more 1:14:56 - The contraction of morbidity that comes with improved healthspan 1:20:56 - Defining healthspan 1:26:14 - Unique perspectives and positive attitudes of centenarians 1:33:32 - Lessons to take away from centenarians 1:38:48 - Metformin overview: history, studies, and potential for gero-protection 1:50:07 - The TAME trial (Targeting Aging with Metformin) 1:59:29 - The challenge of studying metformin in animals models 2:07:27 - How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics 2:14:54 - The search for biomarkers to identify who can benefit from treatment 2:26:29 - The impact of metformin on exercise, and finding the right indication for the use of metformin ​2:39:36 - Are NAD precursors geroprotective? 5 jayalanlife jayalanlife 1 month ago Nir is looking younger with every podcast, maybe he should include skin health. 9 Esmeralda Cole Esmeralda Cole 9 days ago Thanks for the information , very useful! 1 Claudette Sechler Claudette Sechler 3 weeks ago So great! Wonderful guest! Gives me such a perspective on metformin 1 Nahulanham Nahulanham 3 weeks ago What's even more important then what HGH does as it is secreted from the pituitary, is what psychological habits lead to its stimulation or dystrophy. 5 Zandra Rose Zandra Rose 5 days ago Metformin had me seriously planning my suicide. I am so glad I realized it was the drug and not me. 4 Bjarne Tungland Bjarne Tungland 2 days ago Solid podcasting there. Good question about the evidence of metformin, nmn. Ect. Daniel Daniel 2 weeks ago (edited) Maybe we should look into studying taking low-dose methimazole or propylthiouracil in healthy, non-hyperthyorid individuals to see if there is a longevity benefit. 2 M bnto M bnto 1 month ago Question. I’m at minute 12 and 3 hypotheses are suggested: environment, good genes, bad genes. What about the role of stochastic processes in disease, which I understand to be formidable? Maybe centenarians are lucky? 3 Michael Domansky Michael Domansky 2 weeks ago Between taking my Metformin, NAC, Benfotiamine, and Ivermectin I am completely inflammation free! No arthritic limp, no back pain, no bursitis. I take no NSAIDs or Tylenol ! 2 Tim Burke Tim Burke 4 weeks ago Seems like we are better off talking about berberine instead of metformin 18 Chris Purdue Chris Purdue 2 weeks ago Very interesting. My wife was put on Metformin and felt absolutely miserable the entire year that she took it. She was tired all the time which negatively affected her mental health. As soon as she stopped, it went away. 11 Pam Lovell Pam Lovell 2 weeks ago My great aunt who was the eldest child and obese the majority of her adult life lived to 100. Her youngest sibling -- my grandmother the baby of the family-- was thin her entire life died from Alzheimers at age 74. Go figure. 2 Gregory Ludkovsky Gregory Ludkovsky 3 weeks ago Long time no see ! Nice to have you back , Peter Fred Branson Fred Branson 3 weeks ago (edited) Peter please cover SGLT2 for longevity. Metformin is old news. Agree with you in regard to performance athletes or those that focus on exercise. SGLT2, however, extremely interesting for geroprotection (body composition, inflammation, cardio & renal protective). 4 Audrey Hurley Audrey Hurley 4 weeks ago How do I sign up Nir ? I’m interested in getting into your test study, I live Austin, TX area? Is there a study here? 2 Ad Am Ad Am 1 month ago ’As useful as a warm bucket of hamster vomit’ Peter Attia MD Interesting and entertaining as always! Grateful to you, your team, and all the interesting guests! 5 Elizabeth K Elizabeth K 2 weeks ago Couldn't take METFORMIN, so switched to BERBERINE. Works similarly. 2 Joseph1NJ Joseph1NJ 1 month ago So Peter asks If GH was so deadly, where are the bodies? He answered his own question, we just don't have the data. Irish Talks Irish Talks 3 weeks ago What about fertility issues in men taking metformin. Also I feel some of these things talked about could be possibly helped out by doing a carnivore diet. 1 Tim Scannell Tim Scannell 1 month ago Great work 1 Bill99 Bill99 2 weeks ago One question and one comment: Q. I've looked here for the two metformin articles Dr Barzilai referenced to show to our primary care Dr's but can't find them. Any help? Comment: I don't think the Dr's prescribing metformin after reading the articles is still true. I suspect that off label prescriptions for anything are mostly a thing of the past because of the hysteria generated over covid off-labels and the restrictions placed on individual physicians by their practice groups and their malpractice insurers. Fear of malpractice lawsuits has chilled the practice of medicine into paralysis. 1 Tim Burke Tim Burke 1 month ago I've come to the conclusion that this stuff is super complicated and I'm too stupid to understand it all. I'm still gana exercise though. 68 Javad Hashtroudian Javad Hashtroudian 5 days ago My academic background is organic chemistry, biochemistry, and neurochemistry. In my 20s I abused my brain and body through alcohol tobacco and cannabis. I have been a software engineer for 40 years. I still would read biology papers and started intermittent fasting around 2000. In 2012 my GP informed me that tests showed that I was pre-diabetic and pre-hypertensive. Since I don't like drugs that don't get you high I refused pills. I said if I can't control my blood pressure and sugar in 6 months through diet and exercise I'll talk about pharmaceutical intervention. Both my A1C and blood pressure are good now. Now at 75 I don't take any pharmaceuticals while every one of my siblings and cousins take at least one pill a day, some as much as six different pills each day. I do take supplements, intermittent fasting 5 days a week, exercise every day averaging burning 2500 kcals a day, meditate, and have peace and fun. I look much younger than my 75 years and smile a huge amount. I laugh a lot at myself. I believe my attitude keeps me young. My only health concerns are aching knees and peeing many times a night. I discovered that THC-O acetate helps me with urination but gets me high and very tired next day. If I was still a biochemist and had the funding I would do research on THC and TBD derivatives for too much urination. Last point I wish metamorfin was available without prescription. In the meanwhile I have started Berberine and NMN. 1 Borje Lindh Borje Lindh 5 days ago Metformin seems to lower inflammation but also testosterone, growth hormone, mTOR response etc. These things are really good if you for example have cancer. But the same effects also blunt the effects from exercise. So my current understanding is that though metformin is good if you want to get old, but be aware of the side effects. Comments? 1 the future lasts a long time the future lasts a long time 3 weeks ago Can you link the metformin studies, so I can send them to my GP? 1 J. M. J. M. 4 weeks ago Metformin has many great properties, but you don’t want to be on in while you’re building muscle! It promotes AMPK, muscle growth is all about MTor.. Gloria Spau Gloria Spau 4 days ago I am 81 on metformin for one year, lost 15 lb, 5ft 7in , 134, 1000 mil a day, at one time my liver numbers were high, after taking metformin normal, fasting sugar 5.6, not so good rising from sitting position....muscle strength not so good. WorldsBestGuys WorldsBestGuys 3 weeks ago You will know when the longevity research has actually become successful when all of this stuff is censored- the general population will not be allowed to live so long when there’s all these current population related issues, unless there is a need found for them such as slavery. 4 White Ninja White Ninja 1 month ago Peter is profoundly intelligent. I hope he always puts his time to good use. 4 Helen Forrest Helen Forrest 3 weeks ago What about metformin causing severe lactic acid build up and causing many deaths? 2 Nobodyatall Nobodyatall 4 weeks ago Hi Peter, what inhibitors do Nir and you talk about in 14:46 ? ctap inhibitors ? Thanks J K J K 4 weeks ago Excellent Info!!! 1 Tim Burke Tim Burke 1 month ago Do their genes preserve their cardio respiratory health? Are they in the top 3% without exercising? 1 C. Spartacus C. Spartacus 1 month ago Need a TLDR on this one. 2 outofchips outofchips 3 weeks ago Longevity = experience repeated blaney6591 blaney6591 4 weeks ago Episode was confusing and difficult to follow. Can someone post a layman's summary of conclusions drawn? (The link to show notes above only review topics covered, not conclusions). Thanks in advance. 4 Alexis Espinosa Alexis Espinosa 3 weeks ago Will you ever interview Prof. Valter Longo? 5 abdul alamri abdul alamri 4 weeks ago wow, that was sooo intense sandor1969r sandor1969r 3 days ago (edited) The people that lives longer happen to live in places where food is most natural no chemicals like the Hunza tribe for example. Costa Rica has ten times more centenarians than here in USA as Costa Rica food it is reach in nutrients and minerals as they use water that came down from rives near vulcans to irrigates their crops and probably never eat fried food or drink fluoride in water , just two very bad things for the gens. Audrey Hurley Audrey Hurley 4 weeks ago Drs I’ve asked my doctor about prescribing Metformin and rapamycin. Did blood work he stated no diabetes so no need for either. I explained and he knows I’m a care giver with no real caregiver support for myself. Still got no. So would either of you would you prescribe to me? The Calming Gourmet The Calming Gourmet 2 weeks ago According to 23&Me, I'm Ashkenazi. Also, if you look at what the state of my health should be according to 23&Me, I should be a total, overweight mess. It may be "in the genes," but it's mostly up to you. I'm in great shape in spite of what the gene report looks like because of food control. All my immediate family have passed, so I'm doing what i can to see if i can make it to 150 y/o! guy chase guy chase 5 days ago Metformin is toxic to the liver - how can it help with longevity ? ChessMasterNate ChessMasterNate 2 days ago The reason Centenarians are upbeat is because their Amygdala has atrophied. That is the part of our brain that is constantly preparing us to react to negative or dangerous things. Alex Brothers Alex Brothers 1 month ago (edited) Have you ever sat with an "average 95-102" year old? I have and most of them can hardly move and have had enough. Keep your body moving, exercise, ideal body weight and love what you do. 16 Tumble Sensei Tumble Sensei 1 month ago Metformin.. how to stimulate a TON of lactate production quickly. Wow, what a great drug. 1 Bjorsa M Bjorsa M 4 weeks ago You guys are "too harsh on Kersh", if you know what I mean. Pushing