*00:00:36* - Landmark moments in longevity research with the discovery of genes that control the aging process and how these genes can be activated by lifestyle factors such as fasting and exercise. *00:01:06* - Altering the insulin/IGF-1 signaling pathway in earthworms can extend their lifespan by 100%. *00:01:45* - Slowly ageing by design: the rise of NAD+ and sirtuin-activating compounds. *00:05:02* - How resveratrol may delay aging by activating a class of enzymes called sirtuins. *00:06:15* - How the addition of an extra copy of the SIR2 gene in S. cerevisiae (yeast) can extend yeast lifespan by 30%. *00:06:40* - How having high levels of sirtuins may give organisms the benefit of caloric restriction or other stressors such as heat stress or amino acid restriction without actually engaging in those activities. *00:07:50* - How fasting for one or two days per week, a type of intermittent fasting, may activate sirtuins sufficiently to recapitulate the benefits of long-term caloric restriction. Review on caloric restriction and sirtuin biology. *00:08:15* - How the metabolic switch into ketosis may be an important differentiator between ongoing caloric restriction and finite periodic fasts. *00:08:50* - How caloric restriction potently increases sirtuins, as measured by SIRT1 levels, by as much as 5- to 10-fold in the liver and muscle of rats, but this beneficial activity is immediately dampened by the introduction of IGF-1 and insulin. *00:10:13* - How several pathways, including those involving sirtuins, insulin/IGF-1, and mTOR, all interact as components of a highly conserved holistic network to create the benefits of caloric restriction. *00:10:56* - Caloric restriction, fasting, and exercise increase levels of NAD+, and this activates sirtuins. *00:12:20* - NAD+ may regulate circadian rhythm though its control of sirtuins, which in turn regulate both the circadian clock in the brain as well as peripheral clocks, such as the liver. *00:13:00* - In addition to activating sirtuins, NAD+ is essential for mitochondrial metabolism and function but it is also required for repairing damage to DNA by activating an enzyme called PARP. *00:13:30* - How organisms have developed nutrient-sensing genetic pathways such as sirtuins, AMPK, and mTOR in order to understand what is going on in the environment. *00:14:44* - Although NAD+ levels and sirtuin activities decrease with age, animal studies suggest that raising cellular NAD+ levels can trick the body into thinking it is younger. *00:16:00* - Resveratrol enhances the binding of sirtuins to NAD+ thus making sirtuins more easily activated for a longer period. *00:17:28* - How DNA damage consumes NAD+ through the activation of PARP, a major DNA repair protein, leaving less NAD+ available to activate sirtuins and distracting sirtuins from fulfilling their other roles. *00:20:00* - Dr. Sinclair's informational theory of aging posits that aging is due to a loss of cellular identity, a type of epigenetic signal noise, that has parallels in biology with the signal correction capabilities of the TCP/IP protocol. *00:20:33* - Steve Horvath's epigenetic aging clock, which measures DNA methylation groups, may play a role in widespread gene regulation, including sirtuin genes, and how NAD+ may participate in resetting the clock. *00:22:56* - How the epigenetic clock can predict your chronological age and how long you have to live. *00:23:47* - How epigenetic reprogramming in old mice can restore youthful gene activity patterns, reverse the DNA methylation aging clock, and restore the function and regenerative capacity of the aging retina. *00:24:51* - The signal that resets the epigenetic clock in mice involves Yamanaka factors -- a group of four transcription factors that can reprogram an adult cell to become a pluripotent stem cell that can form any cell type. *00:26:24* - How short term treatment with the Yamanaka factors can reverse cellular and physiological hallmarks of aging and prolong lifespan in mice with a premature aging phenotype. *00:27:45* - Dr. Sinclair's hope that we may eventually find a way to induce Yamanaka factors in a way that is more safe and applicable to humans than current genetic engineering and viral techniques used in animal research. *00:28:25* - How fasting, exercise, and other lifestyle factors may slow the rate of epigenetic aging but may not be sufficient to reverse it like some of the powerful Yamanka factors may be able to. *00:29:51* - How Dr. Sinclair's lab and others are trying to find safe ways to reset the epigenetic aging clock with Yamanaka factors without causing tumors and other safety issues. *00:32:46* - How Dr. Sinclair thinks Claude Shannon's theory on mathematical theory communication may also explain the aging process. *00:34:02* - Dr. Sinclair's take on who some of the top scientists to follow in the field of aging epigenetics are, which includes Drs. Juan Carlos Izpisua Belmonte, Steve Horvath, Manuel Serrano, Anne Brunet, Shelley Berger, and Jessica Tyler. *00:36:00* - How nobel-prize winning biologist John Gurdon put an adult cell nucleus from a tadpole into a frog's egg, producing a new tadpole, suggesting that the genome can be reset to a very early stage in an organism's lifespan. Review on nuclear reprogramming. *00:36:22* - How cellular NAD+ is made from a variety of precursors including tryptophan, nicotinic acid, nicotinamide riboside, nicotinamide mononucleotide, and nicotinamide. Nicotinamide riboside gets converted into nicotinamide mononucleotide, which is then converted to NAD+. *00:37:33* - How NAD+ is a large molecule that does not get taken up in animals as efficiently as the NAD+ boosters nicotinamide riboside and nicotinamide mononucleotide, the latter of which is transported by a recently discovered transporter. *00:38:18* - How NAMPT, an enzyme in yeast that is activated by exercise and calorie restriction, is key for NAD+ production and longevity benefits. *00:39:45* - Plants produce compounds that activate sirtuin pathways in plants in response to stress and, in turn, the compounds activate beneficial pathways like the sirtuin pathway in humans, a phenomenon called xenohormesis. Resveratrol is one such compound and is produced when grape plants are stressed either in response to fungus or a lack of water. *00:41:11* - How small stressors such as exercise, calorie restriction, and ingestion of plant polyphenol compounds activate various stress response pathways in the body that help slow aging, but calorie excess and a sedentary lifestyle have the opposite effect, signaling the body to reproduce and continue aging, a concept known as the disposable soma theory of aging. *00:41:56* - When rhesus monkeys were fed a diet high in refined sugar (sucrose) and fat for two years, they experienced a 40% increase in arterial stiffness and inflammation but this was completely reversed if they were given 80 mg of resveratrol per day for one year then 480 mg/day for a second year. *00:44:26* - How resveratrol is a very insoluble molecule but its bioavailability can be increased if it is taken with food that contains a moderate amount of fat. *00:45:38* - Mice that were fed an obesogenic diet but were also given a low dose of resveratrol lived longer and had organs that were healthier and younger looking compared to mice fed the obesogenic diet alone. *00:48:32* - How a phase 2 clinical trial involving people with Alzheimer's disease showed resveratrol improved mental examination status scores, induced marker changes that might suggest reduced accumulation of amyloid-beta in the brain, lowered markers of activated microglia, and more. *00:49:28* - How resveratrol has been shown to induce autophagy by directly inhibiting mTOR through ATP competition in mice. *00:51:00* - How both nicotinamide riboside and nicotinamide mononucleotide have been shown to improve cognitive function and brain pathology in mice that have been engineered to get a disease similar to Alzheimer's disease. 0:51:29 - How treating mice with nicotinamide mononucleotide can prevent age-related endurance losses by promoting new blood vessel growth. *00:52:30* - How an NAD+ isotope tracer study revealed that orally administered precursors of NAD+ such as nicotinamide riboside and nicotinamide mononucleotide do not form NAD+ in any other tissues other than the liver, but that dose was half the amount used in animal studies that showed benefits in the brain and muscle. *00:53:37* - How there may be a threshold dose of nicotinamide riboside and nicotinamide mononucleotide that needs to be crossed in order to override the liver's first pass clearance mechanisms so that nicotinamide riboside and nicotinamide mononucleotide NAD+ levels rise in other tissues like skeletal muscle, and this is why almost all animal studies use very high doses. *00:54:13* - How there may be challenges in translating animal studies on nicotinamide riboside and nicotinamide mononucleotide to humans particularly due to the need to determine the dose required to promote health benefits. *00:56:33* - How a couple of clinical trials are underway to test safety with a molecule called MIB-626, which is a potential strong NAD+ booster. *00:59:16* - Older mice that were given NMN (300 mg/kg/day) experienced delayed aging in the liver, muscle, immune cells, eyes, and bones, but those that took a lower dose of NMN (100mg/kg/day or human equivalent of 8mg/kg/day) had improved mitochondrial function and enhanced physical performance. *01:00:05* - How fragmented sleep consistently leads to higher fasting and postprandial blood glucose levels.
Striking- the level of knowledge these two have and so many actual MD's who barely differentiate between total cholesterol and LDL. Let alone LDL-P small/dense particle size with inflammation. I had a Dr tell me I'm borderline obese. LOL I was a bodybuilder and was right in front of her but she was blinded by BMI categorization. And I paid HER?
@@6789uiop You are a moron if you actually believe this. The amount of information that even a specialized MD has to know is way more broad than these two individuals who specialize in a extremely narrow field. there are a lot of other skills besides textbook knowledge that an MD has to know.. how to operate on a live human, radiation physics, the list goes on. To expect any medical doctor to know about a biochemistry topic as much as a PhD specializing in it is asinine.
@@6789uiop Rhonda Patrick sits at home or in the office for 6 hours reading research papers. Do you think any MD has six hours or even one hour a day to devote to reading research papers? Doctors actually have to see patients and save lives.
Excellent; it gives someone with no background in biochemistry; a fair chance of grasping the concepts you're excited by Rhonda. Those notes on the screen and the time stamps; brilliant! I've heard David Sinclair several times now, but this was the most plausible presentation by far - now I want that book! Thanlyou
Thanks so much, Ron! One thing we've started doing is taking the on-screen notes and breaking them out into a powerpoint presentation for members. This episode alone yielded over 150 slides! Anyone reading this that thinks that might be interesting, please make sure to check out our membership program that offers some great bonuses on our free content, like a monthly Q&A and more. foundmyfitness.com/premium
Very well done! This discussion illustrates why its so helpful to have an interviewer (Patrick) who actually knows the subject matter well enough to keep it at level which is truly informative for reasonably well informed laypeople instead of the boringly simplistic repetitive level of so many others.
Probably the best technical interview that I have ever seen in my life. Sinclair is the master of his field, but Rhonda is so well informed and she handles everything in an excellent manner. She's awesome.
Brilliant. Best aging science dialog I’ve ever heard! Bravo to David Sinclair for his work and for explaining it so lucidly, and bravo to Dr. Patrick for asking such great questions!
This was one of the best interactions I’ve watched yet. Rhonda brought out the best in David. He’s been holding back. We need more like this, other than videos just for beginners.
I shared your excitement as I watched this interview twice - back to back. As if I didn’t already have enough knowledge from your prior outstanding guest interviews. This interview ties together so many loose threads from your previous interviews into a more coherent and workable model of a longevity promoting lifestyle. Year by year, you are creating a magnificent narrative. Thank you for bringing the cutting edge of nutritional research into our living rooms. Long time supporter here.
Thanks so much! I think that's my biggest concern with the depth of our content is that, by digging into so many (albeit important) details, people don't catch the overarching themes. That's really what we're working hard to try to bring together in a way that makes sense and doesn't distort what's represented by the literature.
Hi Rhonda, I have a sulforaphane hack based on grinding broccoli sprout seeds. My grinder broke. I noticed the small pepper container on the counter. The type you purchase that comes with its own little plastic grinder top. I thought "hmmm, the pepper corns look like big broccoli seeds and as a matter of fact the grounded broccoli seeds taste a bit like pepper. I popped the top off the store bought pepper grinder, dumped the seeds and filled it with broccoli seeds. Now I use it as a pepper on my eggs and anything else I can think of....works great! Thanks for all you do Rhonda! I so appreciate your concise delivery of information!
Five star interview. Dr. Patrick is probably the best interviewer in this field. Prof. Sinclair is the leader in this field. I stopped taking NR a couple of years back because of leg cramps a couple of hours before rising. I also have leg cramps on NMN but less often. I would like to hear from others who had cramps. Regards
Well done! I started taking a few supplements three years ago at age 70 - B6, B12, Folate, high dose D with A. Immediately felt better. By "feeling better" I mean this: improved mood, clearer thinking, fewer aches and pains and relief from SAD.Tests revealed the supplements raised B & D in my body from "normal levels" to "optimal levels." Added an NAD supplement two years ago and in a short time felt even better - again using the listed personal criteria. Also noted that almost immediately, BP, which was rising, fell back to normal levels. The effects of supplementing B6, B12, D with A and NAD supplement continue. I believe if this was "placebo effect" the results would have faded. Added 16/8 intermittent fasting three months ago. I feel even better! Dropped 12 pounds and blood glucose dropped from borderline high to normal. A constant from before & throughout this period has been fast-ish walking - 3-6 miles a day. Will be adding Resveratrol (micronized) to this regimen shortly.
Best interview with Dr Sinclair that I have seen since the Peter Attia podcast, loved the level of detail. Looks like I need to move from pure Resveratrol to trans-Resveratrol to harness the full benefit. Also.. FFS re: keeping NMN/NR cold and in the fridge/freezer.
Ya know I've only seen Dr Attia show complete deference to one person, Dr Lustig - high level humility done at complete ease. Did Dr Attia show deference to Dr Sinclair?
You and Dr. David Sinclair are AWESOME! I'm glad that I've found your channel Dr. Patrick! I love what you two are doing. I hope you two keep up the great work with your studies/research. I'd like to see more videos of you and Sinclair and showing the latest studies.
Re: 48:35 the effect of resveratrol on amyloid beta 42 in CSF and an improvement in cognitive function; I don't know how relevant this is, but I recall a paper from about a decade ago saying that resveratrol inhibited the formation of transthyretin amyloid. Supercentenarians typically have a lot of trouble with transthyretin amyloidosis.
Totally appreciative and in awe of the work going into putting the citations in every segment, even with highlights! Thank you so much for making the world a better place ❤
This is an awesome interview she always asks the right questions and gives concise information she has a way of drawing out not only the information from a researcher or doctor, but she imports that information to even the least informed of the people who view these videos and I’m sure they become very well informed after viewing a few of her videos because she’s just a super educational person and a real asset to the field of health anti-aging and general wellness, And what can I say about Dr. Sinclair I think he’s just a marvelous scientist and I am thankful to be alive in such a time as this will affect my future as well
Yes, I take resveratrol in biogel form in a sachet - it's gone through cap-E test as well... showing the high percentage of antioxidants as well in the superfruit product :)
The question I would have liked you ask: If you raise NAD levels by supplement fast and exercise to more youthful levels and then stop supplementing will the NAD levels drop immediately or will you see a gradual decline over years? Impressed by the triage theory, and your further speculating how the body decides on it's priorities on what to fix.I have read Dr Sinclairs book, plus several others in the field.Again very impressed with all your interviews plus your lectures/film on Broccoli and saunas.I know this field did not invent fasting or exercise, and the benefits of Broccoli were already known, but nobody explained Broccoli or saunas and the benefits thereof better than you did.Perhaps you need to write a book? In the books by lots of people there are lots of hacks- but there is one that no one has mentioned and I think it might be something you could take a look at.I'm surprised no one else has spotted it- in the superman book he even has rectal ozone injections! My hack:Massage of the internal organs.As in the liver, kidneys and stomach.
Thank you! On-screen graphics now available as a quick reference powerpoint for members! Learn more about that and a long list of other cool benefits at foundmyfitness.com/premium.
He’s so used to having to present his work in layman’s terms for everyone, he gets so excited when she uses scientific words and he can talk full nerd with her
Just started listening to Dr Rhonda Patrick a little very recently. A video she did on multivitamin supplementation came up, which I just watched. Wow, in a world where people try to misinform the public for ulterior motives, it is both incredibly helpful and encouraging that their are people like you trying to reach out to us with what you genuinely understand to be in our best interests. Look forward to learning much more from you!
I have a suggestion for another interview! Dr. Sinclair could give Dr. Patrick an early copy of his new book soon to come out. Dr. Patrick could familiarize herself with the book and ask Dr. Sinclair questions about it!
It's so great to receive the slides/written info during the talk. I pause and read and then more deeply comprehend what's being said. What an education! Thanks Dr Patrick. If I could have it all my way I'd include a little 'picture in picture' in the bottom right hand corner so we can still see the conversation video on full slide pages.
Thanks so much for letting us know! They are by far one of the most time intensive part of the episodes, but we're getting better at it. One thing we're looking to do is make sure they provide as much value as possible. With that in mind, we've made a new little "benefit" for premium members where they can flip through the graphics as a powerpoint presentation. This episode had over 150 slides! If you're interested in that, you (or anyone reading this) should check out our new premium member option at foundmyfitness.com/crowdsponsor.
Thank you for this presentation. And you put timestamps in for different topics discussed ! You are so thoughtful. I will be coming back to this dialogue again and again.
I’m really hoping we start using these genetic treatments within the next decade, in the 2020s, and not just still talking about it. Life Code. It’s more exciting than computer code.
Hell yeah! I'm quite surprised by how much they seem to have uncovered about the dynamics of the methylation clock of aging! And with AI and more data and research from more labs in the field, it's looking more hopeful than ever right now! And till then, we have time-tested (fasting, cold-water therapy, heat-exposure, exercise, phytochemicals and good diet) and emerging methods of managing aging personally, as shown on this channel.
I'm trying not to be too optimistic about the timeline. NAD precursors, senolytics, healthy diet, exercise and quality sleep may help me live long enough to undergo these types of treatments.
As a little kid, I always wondered why not cure aging and you won't have to worry about 80% of diseases. Microsoft and Apple should be working on aging like they work on I.A., code, and digital advances.
It’s sort of strange that two people this smart chose to sit down for an extended time in the most uncomfortable simple chairs I’ve ever seen. Couldn’t they chose a comfortable chair?
He's on metformin, NR and resveratrol. Not a cure but a pretty good preventive cocktail to decrease damage as we go. You only get metformin by doctors if you have diabetes but the other two you get from walmart :)
A little over my head, but I understand some due to other lecturers and a few books! I will learn more as I follow you two doctors of Philosophy! My newfound interest at 72; never too old to learn! I’ve got your book, Dr. Sinclair...Lifespan!
Anon Bianco it would be interesting to know what those errors are, because just to someone who doesn’t know much about chemistry or genetics etc it just sounds really interesting. So maybe in their enthusiasm they are missing out or glossing over things. Please let us know because this may help others too. Thanks
@@jamesphillips9724 Niagen is NR. NR that has been researched extensively, human/animal trials etc. There's a lot of money behind it. Dr. Sinclair takes NMN but he's very careful not to recommend it over NR. I'm not certain what's going on, could be that because Dr. Sinclair is an inventor of the patent Elysium uses for their NR and has an NMN based supplement he's working on which will likely financially benefit him. Like most companies, Niagen will try to protect their product/image against competitors. All speculation on my part but there's something there and thought it would be funny to joke about.
57:52 - well, crap - doesn't that mean that all the nr and nmn that is commercially available right now is automatically degraded to nicotinamide once it reaches the customer? So we early adopters have all been harming ourselves? I put my nr in the fridge, but didn't think about it allready being degraded at this point from sitting on the shelf for weeks or months before shipping... And I don't know of any manufacturer who stores and/or ships it cooled...
@Mitch Jones Fragile ego I don't know why he keeps saying this as many dispute the need for refrigeration. The folks at Tru Niagen say on their FB page that it's unnecessary. I asked Genex and this was their reply... I think you may be asking this due to the recent interview between Ronda and David. In regards to the NMN cold question, NMN in its raw form is vulnerable and must be kept in a freezer or cold storage. The NMN raw material we use is kept in cold storage all the way up to production. Once the production is completed, it is now stabilized and protected from moisture and light. The product is then kept in a climate-controlled environment. If you listen to the discussion, Sinclair is talking about NMN that if not in a stabilized form, degradation of the product will occur. However, once production is completed, it is then stabilized and protected from light and moisture and has a good shelf life of about 2 years (as long as kept in a cool dry place). Once the bottle is open however, it is now exposed and can start degrading. This is usually not an issue though since the product is a 30 day supply and degradation during that time is minimal. The biggest issue with NMN degrading has to do with moisture, which can cause NMN to breakdown. NMN will hydrolize over-time so it is important to protect it. We include a moisture pack in all our NMN bottles to protect against moisture, and our bottle is opaque, which protects against light. That said, you can store it in your fridge or freezer once you open it if you are more comfortable.
It is always a great advantage when someone like prof. Sinclair is interviewed by an inciteful scientist like Rhonda P. Thank you both for offering this to us all.
Anyone know how long it takes for NMN to degrade if you don’t keep it in the fridge? Seems like that is an important bit of info companies don’t tell you
2-4 weeks depending on the environment it is in. If it is in a dark and non-humid location, it can last longer. If warm and humid, 1-2 weeks. Best to just put it in the fridge when bought. Make a good habit to throw it in the fridge when you get it from the mail. Make sure to get it asap from the mail, because it can degrade in there, as well, depending on the weather. In the winter, doesn't matter. But in the summer, it is best to wait by the window, like a kid and grab it asap and toss it into the fridge.
Rather enjoyed this video. Was very impressed by the thoroughness of the conversation on such a complex and complicated topic. Very exciting research going on!
He never clarified what a 'stabilized' form of NMN would look like. What would one look for to see if they're taking the stabilized form. Is there a way to tell if it is off?
35:35 I'm reading "The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance" by Nessa Carey in 2012. Early in this book, both Dr John Gurdon's and Dr Shinya Yamanaka's 'anti-aging' research is explained. It's very interesting. - Much thanks to my public library for carrying this book 👍👏
22:40: My reaction throughout the video! ^^ 57:52: This! How do you really make sure that your supplements are pristine? How to preserve supplements properly and testing is in need of improvement. 1:09:10: Yeah, same, now with new streetlights outside even my dark curtains that usually kept it near pitch-black don't work. I guess I will get a dark cloth to cover it until I get fitting blinds.
you two together are so fun to watch. This is absolutely incredible research and it seems like every other question Rhonda asks I was want to ask as well. Keep doing these videos and publishing your research. I am so excited!
Dr. Rhonda is fine very likeable lady. Dr. Sinclair is businessman with strong business agenda behind several not proven products. Sort of interesting to listen speculations that should be digested cautiously.
1:00:45 the flushes she talks about is most likely from b3/Niacin (Nicotinic Acid) that one gives flushes on high doses but these flushes are harmless and some people actually like flush effects while others hate them, and new users who don't know about the flush effects often think they are going to die or something like that..
Thats why I subscribed to this channel. Rhonda is so smart and able to get some great detail from Dr. Sinclair other interviewers would not be able to. Very exciting work D. Sinclair is doing. I am not looking to live forever, but would like to live to 100 or 120 and be healthy.
@@rogerbruce2896 Well, I think when you reach that age youll notice that there is a lot more to do and live, so youll want to live a bit more. My grandmother of 90 years is in this process
I've never studied epigenetics (aside from touching on it briefly in my sociology undergrad) but this was all very clear to me, so thanks to both of you for explaining things really well. Also thank you for great subtitles!
I think Rhonda just exposed something here (starts 57:55). He says your NR and NMN should be kept cold. But Rhonda calls him out on the shipping procedure. It seems that they both agree that NMN and NR are not getting shipped cold or at very least they don't know. Actually he says himself he didn't know how it's shipped and Rhonda is saying that it isn't shipped cold. At the very least David doesn't know how his NR/NMN are shipped. So we can't rule out the possibility that it might not have been working for him and he wouldn't know it. This makes it possible that there's some sort of placebo working here and it is working out for him because he thinks so strongly of it.
@@mikelikes3570 Now that I'm thinking about it, I'm assuming he stores his in cold environments, but doesn't know how the rest of the world is getting it whether it's from companies that ship it cold or not cold.
@@lightzaberrr he said in the first JRE that he synthesized enough of it in his lab to last him a life time. So he doesn't buy it from companies. But he didn't mention how he stores it.
He said his lab makes it and he’s happy to send it to other researchers at a subsidised cost. The supplement industry isn’t regulated, I wouldn’t be surprised if half of the nmn supplements is just nicacinamide. The general public definitely wouldn’t know the difference.
@@shockwave1986 Hmm.. haven't seen the entire interview in a while but when does he say that again? The time stamp I mentioned was for the general public and what Ronda was referring to. I don't know how he and his lab ships it themselves to other labs., but if he did, would've found a way to ship it cold to them.
I’ve been using his protocol for 6 weeks. 1 gram mnm 1 gram resvertrol and metformin plus q 10 and policosinol My energy is through the roof considering I’m 51 Ive been working 10 hours a day no breaks for 6 weeks I feel great as soon as I get home I’m out like a light I sleep for 7 hours and wake up without a clock I feel good
I use mnm from Alive by nature on the resvertrol question I use resvertrol from bulksuplements.com they are not a brown color but I’m looking for more info on another source
Intuitive Sean Bulk Supps almost seem too good to be true for the price. It’s also not “Trans” isn’t trans-Resveratrol the type we should use? I also want to know it’s not from China but all of them are probably manufactured there to be realistic
maria G I watched another podcast that was made after this one rhondas was put up late becouse the book has been out for a few months already and they said it was coming out so what I mean to say is in his dr Sinclair recent podcast he said most resvertrol is good mine is almost A white color what I do to make it more absorbable is. I open two capsules into a table spoon and put 2 teaspoons of extra virgin olive oil with it and use a plastic chopstick I stir till de solved and swallow it and chase it with organic apple juice the fat from the olive oil makes it 3 to 5 times more absorbed
Thanks Tom. o/ But I still put mine in the fridge as soon as he mentioned it. ;) Hmn, "stabilised". Sounds comforting. Maybe biochemists know what this means.
I really like that you have found a creative way to utilize the video format by including these snippets of relevant information, diagrams and studies! So far it is unique.
People should be aware that Dr. Sinclair is heavily involved with businesses that sell Nicotinamide Mononucleotide supplements (NMN) ... he has a financial interest in making it seem like the next best thing. I'd be skeptical of what he has to say about that 1 supplement until we see other neutral research coming out on it.
Dr. Sinclair does not have any ties to companies currently selling NMN (or NR) as supplements. It is my understanding that there's a few reasons for some confusion surrounding this for a few reasons: • David holds a patent on Elysium’s Basis product, however he has legally given all financial benefits of this patent to Harvard. • David has co-founded companies in the pharmaceutical space that are currently looking at the efficacy of NMN in FDA clinical trials. That last part may brush a little bit closer to your original point, but also means that by the time David profits from NMN it has to conform to the higher clinical standard of the FDA. In other words, he really doesn't benefit from everyone rushing out and buying NMN supplements on the market right now. You can learn more about David's specific ties here: genetics.med.harvard.edu/sinclair-test/people/sinclair-other.php Also, as pointed out by others, this video is about so much more than NMN and, for the evidence on NMN that we do discuss, we are mostly talking about the specific science that's been through peer review. You'll find almost all of it actually cited in the video, but the specific studies are also linked (by the dozens) on the episode page of our website. Overall, I hope you guys can appreciate this as an extremely objective conversation. Thanks for watching!
What an amazing gentleman doing astonishing work! Thank you for such a fascinating interview which kept me rapt from start to finish. Many screen caps of great plates to study afterwards: must have entailed so much work. Thanks again.
Great talk, but pretty frustrating for those of us taking NR ... so I'm spending $450/ yr taking something that might be doing the exact opposite of what I'm taking it for, and undermining something my diet and exercise choices are aimed at (sirtuin activation) . Great news! : /
After watching both of these scientists on Joe Rogan's podcast, reading their research, watching their videos and reading Dr Sinclair's book I am excited to get some new information. Thank you Dr. Patrick!!
I'd say it's enough to get it from foods that it's found in naturally. Nobody knows if excessive amounts are actually good or not, as there are no longitudinal studies in humans, and it must be 'trans' resveratrol, not 'cis'. Too much of certain things, such as vitamin D3, can be bad.
Check out Joe Rogans podcast with him, he goes into his routine and the supplements be takes. Very briefly he fasts, does high intensity cardio with weights everyday and takes Some super powerful supplements. Some of them you can't buy but some of them are available but pricey.
*00:00:36* - Landmark moments in longevity research with the discovery of genes that control the aging process and how these genes can be activated by lifestyle factors such as fasting and exercise.
*00:01:06* - Altering the insulin/IGF-1 signaling pathway in earthworms can extend their lifespan by 100%.
*00:01:45* - Slowly ageing by design: the rise of NAD+ and sirtuin-activating compounds.
*00:05:02* - How resveratrol may delay aging by activating a class of enzymes called sirtuins.
*00:06:15* - How the addition of an extra copy of the SIR2 gene in S. cerevisiae (yeast) can extend yeast lifespan by 30%.
*00:06:40* - How having high levels of sirtuins may give organisms the benefit of caloric restriction or other stressors such as heat stress or amino acid restriction without actually engaging in those activities.
*00:07:50* - How fasting for one or two days per week, a type of intermittent fasting, may activate sirtuins sufficiently to recapitulate the benefits of long-term caloric restriction. Review on caloric restriction and sirtuin biology.
*00:08:15* - How the metabolic switch into ketosis may be an important differentiator between ongoing caloric restriction and finite periodic fasts.
*00:08:50* - How caloric restriction potently increases sirtuins, as measured by SIRT1 levels, by as much as 5- to 10-fold in the liver and muscle of rats, but this beneficial activity is immediately dampened by the introduction of IGF-1 and insulin.
*00:10:13* - How several pathways, including those involving sirtuins, insulin/IGF-1, and mTOR, all interact as components of a highly conserved holistic network to create the benefits of caloric restriction.
*00:10:56* - Caloric restriction, fasting, and exercise increase levels of NAD+, and this activates sirtuins.
*00:12:20* - NAD+ may regulate circadian rhythm though its control of sirtuins, which in turn regulate both the circadian clock in the brain as well as peripheral clocks, such as the liver.
*00:13:00* - In addition to activating sirtuins, NAD+ is essential for mitochondrial metabolism and function but it is also required for repairing damage to DNA by activating an enzyme called PARP.
*00:13:30* - How organisms have developed nutrient-sensing genetic pathways such as sirtuins, AMPK, and mTOR in order to understand what is going on in the environment.
*00:14:44* - Although NAD+ levels and sirtuin activities decrease with age, animal studies suggest that raising cellular NAD+ levels can trick the body into thinking it is younger.
*00:16:00* - Resveratrol enhances the binding of sirtuins to NAD+ thus making sirtuins more easily activated for a longer period.
*00:17:28* - How DNA damage consumes NAD+ through the activation of PARP, a major DNA repair protein, leaving less NAD+ available to activate sirtuins and distracting sirtuins from fulfilling their other roles.
*00:20:00* - Dr. Sinclair's informational theory of aging posits that aging is due to a loss of cellular identity, a type of epigenetic signal noise, that has parallels in biology with the signal correction capabilities of the TCP/IP protocol.
*00:20:33* - Steve Horvath's epigenetic aging clock, which measures DNA methylation groups, may play a role in widespread gene regulation, including sirtuin genes, and how NAD+ may participate in resetting the clock.
*00:22:56* - How the epigenetic clock can predict your chronological age and how long you have to live.
*00:23:47* - How epigenetic reprogramming in old mice can restore youthful gene activity patterns, reverse the DNA methylation aging clock, and restore the function and regenerative capacity of the aging retina.
*00:24:51* - The signal that resets the epigenetic clock in mice involves Yamanaka factors -- a group of four transcription factors that can reprogram an adult cell to become a pluripotent stem cell that can form any cell type.
*00:26:24* - How short term treatment with the Yamanaka factors can reverse cellular and physiological hallmarks of aging and prolong lifespan in mice with a premature aging phenotype.
*00:27:45* - Dr. Sinclair's hope that we may eventually find a way to induce Yamanaka factors in a way that is more safe and applicable to humans than current genetic engineering and viral techniques used in animal research.
*00:28:25* - How fasting, exercise, and other lifestyle factors may slow the rate of epigenetic aging but may not be sufficient to reverse it like some of the powerful Yamanka factors may be able to.
*00:29:51* - How Dr. Sinclair's lab and others are trying to find safe ways to reset the epigenetic aging clock with Yamanaka factors without causing tumors and other safety issues.
*00:32:46* - How Dr. Sinclair thinks Claude Shannon's theory on mathematical theory communication may also explain the aging process.
*00:34:02* - Dr. Sinclair's take on who some of the top scientists to follow in the field of aging epigenetics are, which includes Drs. Juan Carlos Izpisua Belmonte, Steve Horvath, Manuel Serrano, Anne Brunet, Shelley Berger, and Jessica Tyler.
*00:36:00* - How nobel-prize winning biologist John Gurdon put an adult cell nucleus from a tadpole into a frog's egg, producing a new tadpole, suggesting that the genome can be reset to a very early stage in an organism's lifespan. Review on nuclear reprogramming.
*00:36:22* - How cellular NAD+ is made from a variety of precursors including tryptophan, nicotinic acid, nicotinamide riboside, nicotinamide mononucleotide, and nicotinamide. Nicotinamide riboside gets converted into nicotinamide mononucleotide, which is then converted to NAD+.
*00:37:33* - How NAD+ is a large molecule that does not get taken up in animals as efficiently as the NAD+ boosters nicotinamide riboside and nicotinamide mononucleotide, the latter of which is transported by a recently discovered transporter.
*00:38:18* - How NAMPT, an enzyme in yeast that is activated by exercise and calorie restriction, is key for NAD+ production and longevity benefits.
*00:39:45* - Plants produce compounds that activate sirtuin pathways in plants in response to stress and, in turn, the compounds activate beneficial pathways like the sirtuin pathway in humans, a phenomenon called xenohormesis. Resveratrol is one such compound and is produced when grape plants are stressed either in response to fungus or a lack of water.
*00:41:11* - How small stressors such as exercise, calorie restriction, and ingestion of plant polyphenol compounds activate various stress response pathways in the body that help slow aging, but calorie excess and a sedentary lifestyle have the opposite effect, signaling the body to reproduce and continue aging, a concept known as the disposable soma theory of aging.
*00:41:56* - When rhesus monkeys were fed a diet high in refined sugar (sucrose) and fat for two years, they experienced a 40% increase in arterial stiffness and inflammation but this was completely reversed if they were given 80 mg of resveratrol per day for one year then 480 mg/day for a second year.
*00:44:26* - How resveratrol is a very insoluble molecule but its bioavailability can be increased if it is taken with food that contains a moderate amount of fat.
*00:45:38* - Mice that were fed an obesogenic diet but were also given a low dose of resveratrol lived longer and had organs that were healthier and younger looking compared to mice fed the obesogenic diet alone.
*00:48:32* - How a phase 2 clinical trial involving people with Alzheimer's disease showed resveratrol improved mental examination status scores, induced marker changes that might suggest reduced accumulation of amyloid-beta in the brain, lowered markers of activated microglia, and more.
*00:49:28* - How resveratrol has been shown to induce autophagy by directly inhibiting mTOR through ATP competition in mice.
*00:51:00* - How both nicotinamide riboside and nicotinamide mononucleotide have been shown to improve cognitive function and brain pathology in mice that have been engineered to get a disease similar to Alzheimer's disease.
0:51:29 - How treating mice with nicotinamide mononucleotide can prevent age-related endurance losses by promoting new blood vessel growth.
*00:52:30* - How an NAD+ isotope tracer study revealed that orally administered precursors of NAD+ such as nicotinamide riboside and nicotinamide mononucleotide do not form NAD+ in any other tissues other than the liver, but that dose was half the amount used in animal studies that showed benefits in the brain and muscle.
*00:53:37* - How there may be a threshold dose of nicotinamide riboside and nicotinamide mononucleotide that needs to be crossed in order to override the liver's first pass clearance mechanisms so that nicotinamide riboside and nicotinamide mononucleotide NAD+ levels rise in other tissues like skeletal muscle, and this is why almost all animal studies use very high doses.
*00:54:13* - How there may be challenges in translating animal studies on nicotinamide riboside and nicotinamide mononucleotide to humans particularly due to the need to determine the dose required to promote health benefits.
*00:56:33* - How a couple of clinical trials are underway to test safety with a molecule called MIB-626, which is a potential strong NAD+ booster.
*00:59:16* - Older mice that were given NMN (300 mg/kg/day) experienced delayed aging in the liver, muscle, immune cells, eyes, and bones, but those that took a lower dose of NMN (100mg/kg/day or human equivalent of 8mg/kg/day) had improved mitochondrial function and enhanced physical performance.
*01:00:05* - How fragmented sleep consistently leads to higher fasting and postprandial blood glucose levels.
Thks dude 👍👍👍
Thanks!
Thank you!
Thank you
Legend
This the best David Sinclair interview that I have seen or heard. It really helps when the interviewer has so much knowledge on the subject.
Rhonda is a champion.
I was very dissapointed whith Dr. Sinclairs second JRE apearance. Thank god for this one!
Striking- the level of knowledge these two have and so many actual MD's who barely differentiate between total cholesterol and LDL. Let alone LDL-P small/dense particle size with inflammation. I had a Dr tell me I'm borderline obese. LOL I was a bodybuilder and was right in front of her but she was blinded by BMI categorization. And I paid HER?
@@6789uiop You are a moron if you actually believe this. The amount of information that even a specialized MD has to know is way more broad than these two individuals who specialize in a extremely narrow field. there are a lot of other skills besides textbook knowledge that an MD has to know.. how to operate on a live human, radiation physics, the list goes on. To expect any medical doctor to know about a biochemistry topic as much as a PhD specializing in it is asinine.
@@6789uiop Rhonda Patrick sits at home or in the office for 6 hours reading research papers. Do you think any MD has six hours or even one hour a day to devote to reading research papers? Doctors actually have to see patients and save lives.
My two favorite people talking about the topic aging
Yes mine too! Is there any part where they discuss Sulforaphane?? (Next time they should invite Ben Greenfield to the party :-)
41:46
Sinclair's mice live better than Rhonda Patrick's Mice. Just sayin.
You took the words out of my mouth!
@@koenduindam7764 I would prefer if they invite Peter Attia
Excellent; it gives someone with no background in biochemistry; a fair chance of grasping the concepts you're excited by Rhonda.
Those notes on the screen and the time stamps; brilliant! I've heard David Sinclair several times now, but this was the most plausible presentation by far - now I want that book! Thanlyou
Thanks so much, Ron! One thing we've started doing is taking the on-screen notes and breaking them out into a powerpoint presentation for members. This episode alone yielded over 150 slides! Anyone reading this that thinks that might be interesting, please make sure to check out our membership program that offers some great bonuses on our free content, like a monthly Q&A and more. foundmyfitness.com/premium
Very well done! This discussion illustrates why its so helpful to have an interviewer (Patrick) who actually knows the subject matter well enough to keep it at level which is truly informative for reasonably well informed laypeople instead of the boringly simplistic repetitive level of so many others.
Excellent info from 2 of my fav researchers! Take notes everyone
And Dr. Berry you are one of my favourite doctors.
Since when are people allowed to have fav researchers?
They don't agree with you.
This should be required watching in all high school science class.
My former doctors should watch it!
Why? None of the compounds discussed have any definitive evidence that they work in humans as purported. So far, just hope and optimism.
@@Re3iRtH there is evidence of antiaging but not life Extension, I think.
College students too
@@Re3iRtH Well, I think we can agree that sometimes hope and optimism is what students need to get inspired and pursue a certain path.
I just love David Sinclair. We take NMN and resveratrol since January and can see fantastic results. Thank you David!
Where do you get the supplements? I have a hard time trying to figure out which ones are the best
@@kathleenflatley3973 Hansen Supplements :)
. . . I recently got estimated some 20 (!!) years younger. That feels good !
Intermittent fasting is one of the most effective yet cheapest anti-aging strategy you have
Resveratrol and Pterostilbene
Sounds good but have you tried Cocaine?
@@slavosl4v3s08 Should reservatrol be taken during a fast? or when? I also heard it should be taken with vit C
is 16/8 enough for anti-aging benefits?
@@sirt1353 eat it with fat!
Probably the best technical interview that I have ever seen in my life. Sinclair is the master of his field, but Rhonda is so well informed and she handles everything in an excellent manner. She's awesome.
Another great video from Rhonda "studies have shown" Patrick 😃
Don't you mean Rhonda "That's so cool!" Patrick?
Would you rather listen to info not based on studies and clinical trials?
Brilliant. Best aging science dialog I’ve ever heard! Bravo to David Sinclair for his work and for explaining it so lucidly, and bravo to Dr. Patrick for asking such great questions!
FABULOUS BROADCAST! Please have David back - love your work, Rhonda!
My two favorite people on longevity. Almost hard to decipher the extreme genius. ♥️
This was one of the best interactions I’ve watched yet.
Rhonda brought out the best in David.
He’s been holding back.
We need more like this, other than videos just for beginners.
OMG I'm excited to listen to this!! The whole time listening to him on JRE I was dreaming of a convo between you two.
Same
Hahaha, SAME!
Rhonda thank you for doing these podcasts they are invaluable.
NewbieRN k
I shared your excitement as I watched this interview twice - back to back. As if I didn’t already have enough knowledge from your prior outstanding guest interviews.
This interview ties together so many loose threads from your previous interviews into a more coherent and workable model of a longevity promoting lifestyle.
Year by year, you are creating a magnificent narrative.
Thank you for bringing the cutting edge of nutritional research into our living rooms.
Long time supporter here.
Thanks so much! I think that's my biggest concern with the depth of our content is that, by digging into so many (albeit important) details, people don't catch the overarching themes. That's really what we're working hard to try to bring together in a way that makes sense and doesn't distort what's represented by the literature.
Exactly!!!!
M
.
Hi Rhonda, I have a sulforaphane hack based on grinding broccoli sprout seeds. My grinder broke. I noticed the small pepper container on the counter. The type you purchase that comes with its own little plastic grinder top. I thought "hmmm, the pepper corns look like big broccoli seeds and as a matter of fact the grounded broccoli seeds taste a bit like pepper. I popped the top off the store bought pepper grinder, dumped the seeds and filled it with broccoli seeds. Now I use it as a pepper on my eggs and anything else I can think of....works great! Thanks for all you do Rhonda! I so appreciate your concise delivery of information!
This is the only TH-cam channel I'm scared of missing out.
Wow! Telling sirtuins to stop overworking, wasting energy and go back to where it was 20 years back. I'm so excited.👍 Thank you doctor.
Appreciate all the editing you do for your videos Rhonda!
Five star interview. Dr. Patrick is probably the best interviewer in this field. Prof. Sinclair is the leader in this field. I stopped taking NR a couple of years back because of leg cramps a couple of hours before rising. I also have leg cramps on NMN but less often. I would like to hear from others who had cramps. Regards
Thank you Rhonda and David!! ❤
Well done! I started taking a few supplements three years ago at age 70 - B6, B12, Folate, high dose D with A. Immediately felt better. By "feeling better" I mean this: improved mood, clearer thinking, fewer aches and pains and relief from SAD.Tests revealed the supplements raised B & D in my body from "normal levels" to "optimal levels." Added an NAD supplement two years ago and in a short time felt even better - again using the listed personal criteria. Also noted that almost immediately, BP, which was rising, fell back to normal levels. The effects of supplementing B6, B12, D with A and NAD supplement continue. I believe if this was "placebo effect" the results would have faded. Added 16/8 intermittent fasting three months ago. I feel even better! Dropped 12 pounds and blood glucose dropped from borderline high to normal. A constant from before & throughout this period has been fast-ish walking - 3-6 miles a day. Will be adding Resveratrol (micronized) to this regimen shortly.
Best interview with Dr Sinclair that I have seen since the Peter Attia podcast, loved the level of detail. Looks like I need to move from pure Resveratrol to trans-Resveratrol to harness the full benefit. Also.. FFS re: keeping NMN/NR cold and in the fridge/freezer.
Ya know I've only seen Dr Attia show complete deference to one person, Dr Lustig - high level humility done at complete ease.
Did Dr Attia show deference to Dr Sinclair?
Thanks to David for sharing so much rather early ..that seems like part of the breakthrough; a protocol improvement!
Thanks again Rhonda
You and Dr. David Sinclair are AWESOME! I'm glad that I've found your channel Dr. Patrick! I love what you two are doing. I hope you two keep up the great work with your studies/research. I'd like to see more videos of you and Sinclair and showing the latest studies.
Re: 48:35 the effect of resveratrol on amyloid beta 42 in CSF and an improvement in cognitive function; I don't know how relevant this is, but I recall a paper from about a decade ago saying that resveratrol inhibited the formation of transthyretin amyloid. Supercentenarians typically have a lot of trouble with transthyretin amyloidosis.
Great interview!! Nerver get to comfortable, lift heavy, fast, heat/cold, make interviews on uncomfortable chairs etc.
Totally appreciative and in awe of the work going into putting the citations in every segment, even with highlights! Thank you so much for making the world a better place ❤
This is such a great video. I love how papers relevant to the discussion are shown on the screen in real-time!
I have no idea why I am watching this, I don't understand a word they are saying. Yet it is all strangely mesmerising...
I have been waiting for Patrick to have this discussion with Sinclair and Voila the Magic begins
This the best David Sinclair interview that I have seen or heard. Thank you rhonda.
Check his TED talk he gave in 2013, he actually looks much younger now. I think he is right. These drugs do help.
Its called hair dye :)
I agree. NMN and resveratrol are truly amazing. We take them since January and can see fantastic results
@@katarzynahansen6970 what is NMN?
@@katarzynahansen6970 Which brands are you taking?
😮
@@katarzynahansen6970 what brands
This is an awesome interview she always asks the right questions and gives concise information she has a way of drawing out not only the information from a researcher or doctor, but she imports that information to even the least informed of the people who view these videos and I’m sure they become very well informed after viewing a few of her videos because she’s just a super educational person and a real asset to the field of health anti-aging and general wellness, And what can I say about Dr. Sinclair I think he’s just a marvelous scientist and I am thankful to be alive in such a time as this will affect my future as well
Pumped to check this one out!
Yeah, Mike. Trying to figure this info stacked with your thymus-decay-reversing protocol that sent me down a ribbit hole and brought me here! lol
The most informed interviewer ever 👌
@@mcdonnellpadraic I know, I love it!
Yes, I take resveratrol in biogel form in a sachet - it's gone through cap-E test as well... showing the high percentage of antioxidants as well in the superfruit product :)
This must be the definition of “the perfect duo”
The question I would have liked you ask:
If you raise NAD levels by supplement fast and exercise to more youthful levels and then stop supplementing will the NAD levels drop immediately or will you see a gradual decline over years?
Impressed by the triage theory, and your further speculating how the body decides on it's priorities on what to fix.I have read Dr Sinclairs book, plus several others in the field.Again very impressed with all your interviews plus your lectures/film on Broccoli and saunas.I know this field did not invent fasting or exercise, and the benefits of Broccoli were already known, but nobody explained Broccoli or saunas and the benefits thereof better than you did.Perhaps you need to write a book?
In the books by lots of people there are lots of hacks- but there is one that no one has mentioned and I think it might be something you could take a look at.I'm surprised no one else has spotted it- in the superman book he even has rectal ozone injections!
My hack:Massage of the internal organs.As in the liver, kidneys and stomach.
Excellent discussion, really impressively done with the graphic and citations!
Thank you! On-screen graphics now available as a quick reference powerpoint for members! Learn more about that and a long list of other cool benefits at foundmyfitness.com/premium.
This is by far the most detailed interview with Dr Sinclair that I've come across.
Thanks for the great info!!!
WOW! I need to watch this again when I have time to take notes.
He’s so used to having to present his work in layman’s terms for everyone, he gets so excited when she uses scientific words and he can talk full nerd with her
Just started listening to Dr Rhonda Patrick a little very recently. A video she did on multivitamin supplementation came up, which I just watched. Wow, in a world where people try to misinform the public for ulterior motives, it is both incredibly helpful and encouraging that their are people like you trying to reach out to us with what you genuinely understand to be in our best interests. Look forward to learning much more from you!
I have a suggestion for another interview!
Dr. Sinclair could give Dr. Patrick an early copy of his new book soon to come out.
Dr. Patrick could familiarize herself with the book and ask Dr. Sinclair questions about it!
Great interview Rhonda. I've been waiting for this since January. David is such a classy guy. Thank you.
So pleased that David gave a nod to Claude Shannon. Without Shannons work much of what we have for tech today would not be possible. Cheers
It's so great to receive the slides/written info during the talk. I pause and read and then more deeply comprehend what's being said. What an education! Thanks Dr Patrick. If I could have it all my way I'd include a little 'picture in picture' in the bottom right hand corner so we can still see the conversation video on full slide pages.
Thanks so much for letting us know! They are by far one of the most time intensive part of the episodes, but we're getting better at it. One thing we're looking to do is make sure they provide as much value as possible. With that in mind, we've made a new little "benefit" for premium members where they can flip through the graphics as a powerpoint presentation. This episode had over 150 slides!
If you're interested in that, you (or anyone reading this) should check out our new premium member option at foundmyfitness.com/crowdsponsor.
@@FoundMyFitness Awesome. I'll check out the membership.
Thanks!
Also this is the dream team right here
Thank you for this presentation. And you put timestamps in for different topics discussed ! You are so thoughtful. I will be coming back to this dialogue again and again.
Finally!!! I’ve been waiting for you to post this for AWHILE!!!!! Thanks for doing what you do I’m grateful for you
Wow this was such an incredible interview! Thank you so much for doing this and yes please have David back on as soon as possible! :)
A friend of mine stayed unemployed all his life and looks 40 years younger this does prove stress is an important factor
being unemployed is also a huge stress.
Absolutely amazing presentation. The long wait was worth it.
He is onto something. This stuff will make a old man feel young again. Low dose works very well for me.
I’m really hoping we start using these genetic treatments within the next decade, in the 2020s, and not just still talking about it.
Life Code. It’s more exciting than computer code.
Hell yeah! I'm quite surprised by how much they seem to have uncovered about the dynamics of the methylation clock of aging! And with AI and more data and research from more labs in the field, it's looking more hopeful than ever right now!
And till then, we have time-tested (fasting, cold-water therapy, heat-exposure, exercise, phytochemicals and good diet) and emerging methods of managing aging personally, as shown on this channel.
I'm trying not to be too optimistic about the timeline. NAD precursors, senolytics, healthy diet, exercise and quality sleep may help me live long enough to undergo these types of treatments.
depends who we are using it on lol
As a little kid, I always wondered why not cure aging and you won't have to worry about 80% of diseases. Microsoft and Apple should be working on aging like they work on I.A., code, and digital advances.
This lady is well informed and displined.
It’s sort of strange that two people this smart chose to sit down for an extended time in the most uncomfortable simple chairs I’ve ever seen. Couldn’t they chose a comfortable chair?
The stress from the uncomfortable chairs triggers sirtuins . dont you see 😆
Fernando Almaguer Made me laugh, yeah it keeps you in a low constant state of stress! Haha
@@ryandoherty9696 LOL
Maybe because they both realise that comfort is a mental construct......To be comfortable comes from within.
@@rdallas81 so I should eat a pillow?
Two of my favourite scientists in one video, have can I repay this blessing. 🙏
He's been studying this for 30 years ? Yet he only looks like 35...i guess he found a cure ?!?
Born in 1969.
Beware of Greeks bearing gifts
He does not look 35, he looks 45-50
@@korpen3770 nah...loads of 35 yo that look just like him.
He's on metformin, NR and resveratrol. Not a cure but a pretty good preventive cocktail to decrease damage as we go. You only get metformin by doctors if you have diabetes but the other two you get from walmart :)
A little over my head, but I understand some due to other lecturers and a few books! I will learn more as I follow you two doctors of Philosophy! My newfound interest at 72; never too old to learn! I’ve got your book, Dr. Sinclair...Lifespan!
Outstanding work both! Love your book Dr. Sinclair, your best interview yet Rhonda!
ugh this is so good. l can’t stop watching it. Been rewatching since November.
I suspect the 5 thumbs down people in the first 9 hours didn’t actually listen to this or all of it.
Anon Bianco it would be interesting to know what those errors are, because just to someone who doesn’t know much about chemistry or genetics etc it just sounds really interesting. So maybe in their enthusiasm they are missing out or glossing over things. Please let us know because this may help others too. Thanks
Niagen groupies
J. Boogie I had to google that, it’s expensive. I didn’t hear them mention that, are they paid by them?
@@jamesphillips9724 Niagen is NR. NR that has been researched extensively, human/animal trials etc. There's a lot of money behind it. Dr. Sinclair takes NMN but he's very careful not to recommend it over NR. I'm not certain what's going on, could be that because Dr. Sinclair is an inventor of the patent Elysium uses for their NR and has an NMN based supplement he's working on which will likely financially benefit him. Like most companies, Niagen will try to protect their product/image against competitors. All speculation on my part but there's something there and thought it would be funny to joke about.
Anon Bianco thanks I agree
So amazing you both put the full episode and broke it down into useful clips. Please give a bonus to whomever thought of that!
57:52 - well, crap - doesn't that mean that all the nr and nmn that is commercially available right now is automatically degraded to nicotinamide once it reaches the customer? So we early adopters have all been harming ourselves? I put my nr in the fridge, but didn't think about it allready being degraded at this point from sitting on the shelf for weeks or months before shipping...
And I don't know of any manufacturer who stores and/or ships it cooled...
Didnt he say it's only sensitive to light? Or did I miss the cold part
@Mitch Jones Fragile ego I don't know why he keeps saying this as many dispute the need for refrigeration. The folks at Tru Niagen say on their FB page that it's unnecessary. I asked Genex and this was their reply...
I think you may be asking this due to the recent interview between Ronda and David. In regards to the NMN cold question, NMN in its raw form is vulnerable and must be kept in a freezer or cold storage. The NMN raw material we use is kept in cold storage all the way up to production. Once the production is completed, it is now stabilized and protected from moisture and light. The product is then kept in a climate-controlled environment. If you listen to the discussion, Sinclair is talking about NMN that if not in a stabilized form, degradation of the product will occur. However, once production is completed, it is then stabilized and protected from light and moisture and has a good shelf life of about 2 years (as long as kept in a cool dry place). Once the bottle is open however, it is now exposed and can start degrading. This is usually not an issue though since the product is a 30 day supply and degradation during that time is minimal. The biggest issue with NMN degrading has to do with moisture, which can cause NMN to breakdown. NMN will hydrolize over-time so it is important to protect it. We include a moisture pack in all our NMN bottles to protect against moisture, and our bottle is opaque, which protects against light. That said, you can store it in your fridge or freezer once you open it if you are more comfortable.
And here's a link where they did testing on NMN over time
www.garmaonhealth.com/is-your-nmn-supplement-safe-and-potent/
It is always a great advantage when someone like prof. Sinclair is interviewed by an inciteful scientist like Rhonda P.
Thank you both for offering this to us all.
Christos Saripanidis I think you meant insightful not inciteful😊
@@swisstrader Oh Yes I Do! (omg: The wonders of Grammarly)
Anyone know how long it takes for NMN to degrade if you don’t keep it in the fridge? Seems like that is an important bit of info companies don’t tell you
2-4 weeks depending on the environment it is in. If it is in a dark and non-humid location, it can last longer. If warm and humid, 1-2 weeks. Best to just put it in the fridge when bought. Make a good habit to throw it in the fridge when you get it from the mail. Make sure to get it asap from the mail, because it can degrade in there, as well, depending on the weather.
In the winter, doesn't matter. But in the summer, it is best to wait by the window, like a kid and grab it asap and toss it into the fridge.
Rather enjoyed this video. Was very impressed by the thoroughness of the conversation on such a complex and complicated topic. Very exciting research going on!
The awkward silence just after the intro is pretty funny.
I am so happy both of these people got to meet!
He never clarified what a 'stabilized' form of NMN would look like. What would one look for to see if they're taking the stabilized form. Is there a way to tell if it is off?
Did you find a answer for your question?
35:35 I'm reading "The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance" by Nessa Carey in 2012. Early in this book, both Dr John Gurdon's and Dr Shinya Yamanaka's 'anti-aging' research is explained. It's very interesting.
- Much thanks to my public library for carrying this book 👍👏
22:40: My reaction throughout the video! ^^
57:52: This! How do you really make sure that your supplements are pristine? How to preserve supplements properly and testing is in need of improvement.
1:09:10: Yeah, same, now with new streetlights outside even my dark curtains that usually kept it near pitch-black don't work. I guess I will get a dark cloth to cover it until I get fitting blinds.
you two together are so fun to watch. This is absolutely incredible research and it seems like every other question Rhonda asks I was want to ask as well. Keep doing these videos and publishing your research. I am so excited!
Dr. Rhonda is fine very likeable lady. Dr. Sinclair is businessman with strong business agenda behind several not proven products. Sort of interesting to listen speculations that should be digested cautiously.
This Guy feels off
1:00:45 the flushes she talks about is most likely from b3/Niacin (Nicotinic Acid) that one gives flushes on high doses but these flushes are harmless and some people actually like flush effects while others hate them, and new users who don't know about the flush effects often think they are going to die or something like that..
When the interviewer can go toe-to-toe with the expert.
Thats why I subscribed to this channel. Rhonda is so smart and able to get some great detail from Dr. Sinclair other interviewers would not be able to. Very exciting work D. Sinclair is doing. I am not looking to live forever, but would like to live to 100 or 120 and be healthy.
@@rogerbruce2896 Well, I think when you reach that age youll notice that there is a lot more to do and live, so youll want to live a bit more. My grandmother of 90 years is in this process
I've never studied epigenetics (aside from touching on it briefly in my sociology undergrad) but this was all very clear to me, so thanks to both of you for explaining things really well. Also thank you for great subtitles!
I think Rhonda just exposed something here (starts 57:55). He says your NR and NMN should be kept cold. But Rhonda calls him out on the shipping procedure. It seems that they both agree that NMN and NR are not getting shipped cold or at very least they don't know. Actually he says himself he didn't know how it's shipped and Rhonda is saying that it isn't shipped cold. At the very least David doesn't know how his NR/NMN are shipped. So we can't rule out the possibility that it might not have been working for him and he wouldn't know it. This makes it possible that there's some sort of placebo working here and it is working out for him because he thinks so strongly of it.
that is, unless it didnt turn brown?
@@mikelikes3570 Now that I'm thinking about it, I'm assuming he stores his in cold environments, but doesn't know how the rest of the world is getting it whether it's from companies that ship it cold or not cold.
@@lightzaberrr he said in the first JRE that he synthesized enough of it in his lab to last him a life time. So he doesn't buy it from companies. But he didn't mention how he stores it.
He said his lab makes it and he’s happy to send it to other researchers at a subsidised cost. The supplement industry isn’t regulated, I wouldn’t be surprised if half of the nmn supplements is just nicacinamide. The general public definitely wouldn’t know the difference.
@@shockwave1986 Hmm.. haven't seen the entire interview in a while but when does he say that again? The time stamp I mentioned was for the general public and what Ronda was referring to. I don't know how he and his lab ships it themselves to other labs., but if he did, would've found a way to ship it cold to them.
I’ve been using his protocol for 6 weeks. 1 gram mnm 1 gram resvertrol and metformin plus q 10 and policosinol My energy is through the roof considering I’m 51 Ive been working 10 hours a day no breaks for 6 weeks I feel great as soon as I get home I’m out like a light I sleep for 7 hours and wake up without a clock I feel good
I've been looking up a bunch of resveratrol products online, how do you make sure they haven't been damaged by UV light?
I use mnm from Alive by nature on the resvertrol question I use resvertrol from bulksuplements.com they are not a brown color but I’m looking for more info on another source
You’re on the same protocol as myself. Even same ABN for NMN. Today is my 62nd bday and I feel terrific. Good luck to you sir
Intuitive Sean Bulk Supps almost seem too good to be true for the price. It’s also not “Trans” isn’t trans-Resveratrol the type we should use? I also want to know it’s not from China but all of them are probably manufactured there to be realistic
maria G I watched another podcast that was made after this one rhondas was put up late becouse the book has been out for a few months already and they said it was coming out so what I mean to say is in his dr Sinclair recent podcast he said most resvertrol is good mine is almost A white color what I do to make it more absorbable is. I open two capsules into a table spoon and put 2 teaspoons of extra virgin olive oil with it and use a plastic chopstick I stir till de solved and swallow it and chase it with organic apple juice the fat from the olive oil makes it 3 to 5 times more absorbed
I reached out to alive by nature and they told me that their NMN is stabilized and can be stored at room temperature.
Tom Woodall i store mine at room temps
Tom Woodall thought he was talking about NR
Thanks Tom. o/ But I still put mine in the fridge as soon as he mentioned it. ;) Hmn, "stabilised". Sounds comforting. Maybe biochemists know what this means.
GM4ThePeople same
I really like that you have found a creative way to utilize the video format by including these snippets of relevant information, diagrams and studies! So far it is unique.
People should be aware that Dr. Sinclair is heavily involved with businesses that sell Nicotinamide Mononucleotide supplements (NMN) ... he has a financial interest in making it seem like the next best thing. I'd be skeptical of what he has to say about that 1 supplement until we see other neutral research coming out on it.
What brand name is he selling under? I could not find it. I thought he said on Rogan he does not sell any.
NMN/NAD depletes the methyl components and can cause greater harm than good. Too much wishful thinking. There is no magic ambrosia.
This statement is completely untrue.
Dr. Sinclair does not have any ties to companies currently selling NMN (or NR) as supplements. It is my understanding that there's a few reasons for some confusion surrounding this for a few reasons:
• David holds a patent on Elysium’s Basis product, however he has legally given all financial benefits of this patent to Harvard.
• David has co-founded companies in the pharmaceutical space that are currently looking at the efficacy of NMN in FDA clinical trials.
That last part may brush a little bit closer to your original point, but also means that by the time David profits from NMN it has to conform to the higher clinical standard of the FDA. In other words, he really doesn't benefit from everyone rushing out and buying NMN supplements on the market right now.
You can learn more about David's specific ties here: genetics.med.harvard.edu/sinclair-test/people/sinclair-other.php
Also, as pointed out by others, this video is about so much more than NMN and, for the evidence on NMN that we do discuss, we are mostly talking about the specific science that's been through peer review. You'll find almost all of it actually cited in the video, but the specific studies are also linked (by the dozens) on the episode page of our website. Overall, I hope you guys can appreciate this as an extremely objective conversation. Thanks for watching!
What an amazing gentleman doing astonishing work! Thank you for such a fascinating interview which kept me rapt from start to finish. Many screen caps of great plates to study afterwards: must have entailed so much work. Thanks again.
Michael James I totally agree. These are the real deal, both!
Great talk, but pretty frustrating for those of us taking NR ... so I'm spending $450/ yr taking something that might be doing the exact opposite of what I'm taking it for, and undermining something my diet and exercise choices are aimed at (sirtuin activation) . Great news! : /
Not working at all likely.
For 125.00 a month you can take the nfr1 and nfr2, the NAD
@1234 ... Yep.
After watching both of these scientists on Joe Rogan's podcast, reading their research, watching their videos and reading Dr Sinclair's book I am excited to get some new information. Thank you Dr. Patrick!!
Praise the gods for youtube channels, so I can pretend like I have very well educated, interesting, and "normal" friends to "converse" with.
Her excitement made excitement pour out of me
Great Interview . Thank You Rhonda.
Thanks Rhonda and David - Really grateful to both of you for sharing the amazing work you do
Rhonda is so freakin funny 😂..together with incredible knowledge, always makes these interviews even better than most.
Beauty, brains, and humor, what a combo!
David is another of Australia's great exports. Clever bloke!
All the resveratrol I've seen is brown. Anyone know of a 'non-degraded' source/brand?
I'd say it's enough to get it from foods that it's found in naturally. Nobody knows if excessive amounts are actually good or not, as there are no longitudinal studies in humans, and it must be 'trans' resveratrol, not 'cis'. Too much of certain things, such as vitamin D3, can be bad.
Check out resveratrol by "Toniiq" brand on Amazon. I spent last night looking at all the options available and this (more costly) one seemed best.
@@Uber_Xeno looks like a good option, thanks
I really do appreciate that you include the related publications and figures during the video. I hope more will follow your example!
I'd like to know his personal protocol for fasting and diet (without giving medical advice)
Check out Joe Rogans podcast with him, he goes into his routine and the supplements be takes. Very briefly he fasts, does high intensity cardio with weights everyday and takes Some super powerful supplements. Some of them you can't buy but some of them are available but pricey.
He summarizes his routine in his book as well.
It is published somewhere on internet. I stumbled upon artice, covering his routine, I bet that you can find it if googling it
Clayton Blythe I think he does mostly OMAD, sometimes two within a 4-6 hr window. He’s eat a low carb diet high in vegetables, and some protein.
Finally, they both speak. Great job Rhonda 💪😊