TIMELINE... • 00:03:22 - How genetically inhibiting autophagy actually increases cellular sensitivity to death and how this was counterintuitive because autophagy was thought, at one time, as a type of activity predominantly concerned with actually initiating cell death. • 00:04:44 - The external signals causing autophagy. • 00:05:29 - The role of growth factors in transporting nutrients from the outside world into the intracellular space. • 00:05:48 - Autophagy as a process that destroys bioenergetic macromolecular reserves including proteins, lipids, and nucleic acids to generate energy. • 00:06:28 - How declines in the ATP (energetic) status of the cell trigger autophagy by increasing the activity of a pathway known as AMP Kinase. • 00:06:36 - How reductions in the cytosolic pool of acetyl-CoA as a consequence of reductions in glycolysis, amino acid catabolism, or beta-oxidation, ultimately result in the de-acetylation of hundreds of cellular proteins involved in autophagy. Nutrient deprivation → ↑ Protein Deacetylation (↓ cytosolic Acetyl CoA) + ↓ mTOR + ↑ AMP Kinase → Autophagy • 00:09:37 - The role of the inhibition of mTOR and activation of AMP Kinase in cellular autophagy. mTOR is a pathway robustly activated by IGF-1 and associated with increases in cell growth, proliferation, motility and protein synthesis. AMP Kinase, on the other hand, is a pathway important in regulating cellular energy homeostasis by inhibiting synthesis of fatty acids and triglycerides and activating fatty acid uptake and beta-oxidation in the liver. • 00:09:37 - The indirect relationship between protein acetylation status (and cytosolic acetyl CoA availability) and the suppression of mTOR and activation of AMP Kinase in cellular autophagy. • 00:10:23 - The possibility of using selective nutrient restriction as an autophagy-inducer instead of more generalized nutrient deprivation or fasting. • 00:11:11 - Cytoplasmic protein deacetylation as a potential surrogate marker for fasting-induced autophagy (still undergoing validation) but possibly not other forms of autophagy, such as the kind pharmacologically induced by interaction with a protein involved in vesicle-trafficking processes called Beclin 1. • 00:12:53 - How a protein called LC3 associate with structures called autophagosomes to facilitate autophagy in response to deacetylation it undergoes. Note: this sirt1-mediated deacetylation of LC3 is induced as an important response to cell starvation. • 00:14:22 - The special flow cytometry needed in order to measure some of the proteins associated with the activation of autophagosomes in autophagy. • 00:15:04 - The desirability of being able to know and test whether or not your fasting is triggering robust autophagy or not. • 00:16:30 - The minimum amount of fasting necessary to activate autophagy. • 00:16:56 - Whether or not time-restricted eating or 16:8 intermittent fasting reliably induces autophagy in any of our tissues. • 00:17:57 - The important differences between prolonged fasting in humans and the rodent animal models used in studies. • 00:19:03 - The ~12-hour half-life of IGF-1 and whether or not that has any implications for the potential of autophagy in shorter duration fasts. • 00:20:12 - The effects of long-term caloric restriction on markers of cellular autophagy in humans. • 00:21:32 - The effect of an every-other-day eating pattern in rodents and how this pattern actually mimics the longevity producing effects of caloric restriction but with the advantage of stabilizing long-term at a more normal body weight. (Note: Dr. Kroemer is quick to point out that this type of intermittent fasting is more dramatic than it would be in humans because of differences in metabolism… the animals actually experience a 10% oscillation in body weight from this pattern!) • 00:24:35 - The effect of exercise (especially endurance exercise) on autophagy in muscle tissue. • 00:25:08 - The role of autophagy as a mediator of the anti-obesity and anti-diabetic effects of endurance exercise. • 00:26:58 - The differences between macroautophagy, microautophagy, and chaperone-mediated autophagy. • 00:28:03 - The difference between autophagy that is dictated by demand (nutrient stress) versus autophagy that occurs as the need arises to recycle damaged organelles. • 00:28:40 - How damaged organelles change the composition of their surfaces in order to decorate them with signals for the stimulation of their engulfment by the autophagosome. • 00:29:07 - The many, many names autophagy has when we are talking about it in the context of specific macromolecular structures and organelles (e.g. mitophagy for mitochondria, pexophagy for peroxisomes, reticulophagy for endoplasmic reticulum, ribophagy for ribosomes, and virophagy for viruses). • 00:29:35 - How autophagy from nutrient deprivation still prefers to first recycle organelles that have been slightly marked… in other words, that are already aged or slightly damaged. • 00:31:15 - How mitochondrial use ubiquitination, a process which occurs when these organelles begin to lose their membrane potential, in order to signal damage and to ensure preferential targeting by the autophagic machinery. ↓ mitochondrial transmembrane potential → ↑ ubiquitination → ↑ mitophagy • 00:32:42 - The coordinated manner in which mitophagy and mitochondrial biogenesis act together in a closed feedback loop in order to preserve mitochondrial quality while preserving the total pool of functioning mitochondria. • 00:33:34 - The changes that can occur in total mitochondrial pool as cells adapt to take on new metabolic profiles through a mitophagy-mediated process. This can occur as cells differentiate into new cell types that are specialized for glycolytic energy generation. • 00:35:13 - The role autophagy plays in the prevention of neurodegenerative diseases caused by protein aggregates. • 00:37:18 - How autosomal recessive mutations (where both parents must contribute a defective gene for PD to arise in the offspring) in a kinase protein called PINK1 disrupts its ability to recruit a protein called Parkin that mediates the targeting of mitochondria for mitophagy. ↓ PINK1’s kinase activity → ↓ parkin recruitment → ↓ mitophagy → ↑ accumulation of damaged mitochondria • 00:38:01 - Mitochondrial membrane permeabilization as a death signal due to the release of dangerous proteins contained in the mitochondria. • 00:39:05 - Dr. Valter Longo’s research demonstrating a cycle of prolonged fasting followed by a refeeding can recycle 28% of the white blood cells, and reduce the severity of an autoimmune disease (multiple sclerosis). • 00:39:52 - The evolutionarily-conserved sickness response (food avoidance) as a way of beneficially altering immune responses through through altered metabolism and autophagy. • 00:41:02 - The surprising increase in lethality that happens when mice are force fed (glucose in this case) while exhibiting sickness response from a bacterial challenge. • 00:42:27 - The effects of an anti-malarial known as chloroquine which has some cytotoxic effects in cancer cells, but is actually (surprisingly) an inhibitor of autophagy. • 00:43:12 - Studies of the lysosomal disrupter and anti-malarial chloroquine in combination with chemotherapy in the treatment of cancer. • 00:44:04 - The differential roles autophagy plays in the progression of cancer in pre-malignant cells, when it is suppressed, versus in malignant cells, when it is sometimes used as an adaptation helpful to the survival of malignant cells experiencing environmental stress. ↓ tumor suppressor gene activity → ↓ autophagy → survival of pre-malignant cells → ↑ autophagy as a malignant adaptation • 00:44:49 - How inhibition of autophagy by itself is sufficient to induce oncogenesis, particularly in leukemia. • 00:48:10 - How cells undergoing autophagy can release ATP into the extracellular space where it can function as a signal that recruits and activates immune cells against tumor antigens through the activities of purinergic receptors. ↑ autophagy → ↑ extracellular ATP → activation of purinergic receptor-mediated immunosurveillance • 00:48:49 - The importance of the triggering of this immunosurveilance system as part of the cell death associated with chemotherapy. • 00:50:27 - The class of compounds known as “caloric restriction mimetics” that affect autophagy by perturbing various pathways in such a way as to reductions in cytosolic acetyl CoA and protein deacetylation in a manner similar to nutrient deprivation. Examples include: hydroxycitrate (inhibits ATP citrate lyase), spermidine (inhibits Ep300, a protein acetyltransferase), and resveratrol (activates deacetylases). • 00:55:27 - How intestinal bacteria may produce as much as 1/3rd of the body’s spermidine and how this production rate can be manipulated by probiotic and dietary interventions. • 00:56:17 - How the ability of caloric restriction mimetics (CRMs) to induce a type of autophagy that provokes immunosurveillance potentially offers an opportunity for synergy when used in combination with chemotherapeutic agents in the treatment of cancer. • 00:56:56 - How the inhibition of autophagy in malignant cells or destruction of the extracellular ATP released by cells undergoing autophagy is able to abolish the favorable interaction between caloric restriction mimetic drugs and chemotherapy. • 00:58:02 - The tendency for dietary consumption of caloric restriction mimetics, particularly hydroxy citrate, to induce autophagy and reduce weight gain in mice fed an obesogenic diet. • 00:59:17 - Dr. Kroemer’s personal intermittent and prolonged fasting practices and his habit of consuming foods that may contain some natural quantities of caloric restriction mimicking compounds. • 01:01:40 - The autophagy-enhancing effect of coffee (with and without caffeine).
Trinitrophenylnitramine It's complicated. But RT has been found to actually stimulate autophagy if I'm not mistaken. in fact I just Googled resistance training and autophagy and a few studies came up instantly showing how resistance training stimulates autophagy and how autophagy plays a role in the performance and training adaptations. I like to think of it this way yes resistance training increases igf-1, but I think it may be dose-dependent. And if you think about it resistance training initially is catabolic because it breaks down muscle tissue and then when we recover, it rebuilds. Endurance exercise definitely stimulates autophagy.
27:04 on the possible synergy between fasting and exercise: the paper your cited just before www.researchgate.net/publication/276066849_Activation_of_autophagy_in_human_skeletal_muscle_is_dependent_on_exercise_intensity_and_AMPK_activation seems to examine exactly that. It showed that intensity of concentric exercise more than feeding state is correlated to autophagy. If I understand the paper correctly.
FoundMyFitness Dr. Patrick.. Do you think autophagy will also consume THC metabolites and allow rapid THC detox for people who have smoked pot? The problem THC metabolites are fat soluble and store themselves in fat for to be slowly detoxed over time.
Amazing that the sum total of human knowledge and the latest research is at our fingertips. Still, people need to make the effort to be their own best advocates for their health instead of medical industry shills that put profits before people.
This knowledge has been around for centuries! lol But people don't like 'popular wisdom' and think science figures things out... Which yeah is an healthy way to have about things... Because it's better to have prove than just words... But the non laboratory scientists are not that dumb. They have a sense of what's going on. Even religion has a commandment for gluttony for example. So 2000 years ago they're already talking about this at least!
And yet so many stupid people still around that believe God cursed all of His Creation to dreadful pain and excruciating suffering just because one guy ate a piece of fruit thousands of years ago!
How intelligent is this guy! Wow, a knockout interview. Also, I can tell you took the time to edit the closed captioning, which isn't easy or quick. Wanted to express my appreciation for that, because having captions on helps me concentrate and retain information. Thank you for producing all these high quality, informative videos.
Thank you for the nice note! The whole transcript is also posted on the episode page on the website at foundmyfitness.com/episodes/guido-kroemer. Moreover, they're searchable at foundmyfitness.com/search.
@@FoundMyFitness I TOTALLY CONCUR with Tyanite about the benefit of the closed captions, without which I CANNOT watch this, or any other, vid, 'cause I'm nearly deaf. The fact that the auto-generated captions being edited is a huge WOW for me; and on top of that, there' is a freak'n TRANSCRIPT of this vid! It does not get better than this for deaf people! THANK YOU SO MUCH, Rhonda! You are a true HERO to many!
Rare to find a raw , unfiltered podcast that focuses on the science , without dumbing it down to pander to the audience. I didn't understand a lot of the cellular mechanisms entirely , but the numerous papers being cited, motivate me enough to find out. Dr Guido seems like on of the most knowledgeable persons I've seen on your podcast, its impressive to hear the breadth of his knowledge. P.S Spermidine in cheese in synergy with resveratrol in wine , would be interesting to see if this is a reason behind the French longevity paradox.
I agree with you, just keep in mind that to intelligently decide what you believe you need to have an understanding of research. You need to decide for yourself whether or not you believe the studies cited truly prove the speakers point and how strongly. Personally I remain skeptical in most cases even if I am convinced enough to apply what someone is saying.
Fantastic interview, even more remarkable when you think that English is the second language from Dr Kroemer! He speaks better English than most of us native speakers. I find that the people with the most knowledge and intelligence are very calm and don't let their emotions get involved with their answers. I didn't understand everything he was talking about but bit by bit, I am getting very interested in fasting and autophagy. When a man like Dr.Kroemer is on OMAD plus prolonged fasting, not to mention wine and cheese! That is good enough for me Thanks and keep them coming!
Top 10, or even 5 here Rhonda, this was an exceptional interview! There is beauty in science, you know how to waltz with intellects and match them step for step. There were so many "connect the dots" moments for me in this one, I'm sharing it far and wide, and coming back for the encore. Bravo, and many thanks to Guido for coming on, he clearly appreciated your considerate, intelligent interview style. So grateful for your work, thank you.
People who attend Trump rallies think that Dr Fauci speaks in a high scientific register. No, he does not. _This_ is the full meal deal and I'm loving every minute.
Nice job Dr. Patrick, your videos are getting better and better :) The extra multimedia inserts make these things so much easier to understand for the rest of us.
My thinking is that Dr. Patrick is pretty humble. I feel fortunate every time I watch one of her videos on whatever subject I have ‘searched out.’ She’s like a modern-day Leonardo DV that we get to watch on you.tube🇺🇸
Great video! Have been following you since I came across your lecture on hypothermic conditioning and epigenetic mechanisms. You have a great way of expressing information so it's easily understood. I have put your science into practice and have seen tremendous results at 39. Eating 1 meal a day for 7 months I've lost 45lbs and gained a whopping 18lbs of lean muscle mass. After around 18hrs my t levels and igf-1 literally go through the roof so it feels. I hope you read this because I really want express my gratitude for your work and helping people. Great work Dr Patrick!
Thank you so much! So much time you must have spent putting all of this together. Pro tip:I watch this on my phone and tablet at the same time so I can pause the pictures and articles. Probably because I’m slow and need more autophagy in my life.
I had such bad breakouts (often around my chin, jawline, neck) as my hormones began changing in my 40's. It was so aggravating, but things leveled out and my skin is usually clear now! Just in time for deeper wrinkles and sagging...😅 You're so young and gorgeous! I can't wait to try these techniques!❤
Huge thanks for you and your team offering the non-academic interested audience the latest progress on research, and these amazing illustration is pulling us to keep up, This channel offers one of the most professional and responsible content in this field; big thanks and respect
I love how this gives me so much information. How great it is to be living in a time with this much information out there and the difference between of opinions on this subject. It’s great!!!
Like at least one other commenter, down below, I fast 15 - 16 hours every day. My morning workout comes just before breakfast. Except, I've been doing this four years. I'm almost never hungry, no matter what time of day, and at 67, I don't have much gray hair (which is said to be caused by senescent cells around the hair follicles). As Dr. Ohsumi said in one of his lectures, during complete cellular autophagy, about half the cells consumed are healthy and about half are unhealthy (usually senescent). And as we all believe we know, senescent cells are the bad guys. The body keeps cells around that it would normally kill and eat. But if the body isn't hungry, it keeps these for a snack "later." Very often, "later" never arrives. I don't like working out after a meal, so I work out in the mornings, before breakfast, when my stomach is fairly down to empty. I always have tons of energy and more to spare. I'm also deeply engaged in a ketogenic diet (low carb, low protein, high fat). I'm surprised, over the last four years, that the more fat in my diet, the more weight I've lost. It also appears that, if you don't give your body enough energy to function, it will break down protein and turn it, essentially, into carbs. One day recently, after a bike ride, a friend pulled out some meaty treats (slim jim style - I said they look like doggie treats) and offered me some. I mansplained this to her and said, "you may as well be eating potato chips." She said, "Nu uh." I said, "Uh huh." And that went on a few rounds. But we know that carb burners need energy every two hours or they get hungry. Fat-adapted folk can go for a fairly long while (days, weeks, months) without food, and never get hungry. At the end of a 16 hour fast, you're burning fat (there are no carbs left in your stomach to burn). My most recent blood tests were pretty amazing, so I'm fairly enamored of this diet. I'm always eating the tastiest, fattest, richest, saltiest delicious diet imaginable (I use potassium-sodium 50-50 salt), with almost no carbs, and somewhat low protein. I only eat two meals a day and they're fairly small. I can't seem to fit a third meal (lunch) in. It's just breakfast and dinner.
I would like to offer my sincere thanks for this incredible information. It was so interesting to listen to and extremely helpful. I am going to start implementing 3 days water fasts every month for the autophagy benefits now!!
So....we now know...that beyond the Lysosome...that we've known about for 30 years...that we have an endometabolic mechanism to "clean ourselves out; intracellularly for our recapturing of said proteins/amino acids for the resequestering of our own reuse. This explains alot,....as related to our ability to fast for many days, weeks,...and even months when "food" is not available..or for our own 'desire' to readapt our inherent cellular mechanism back what may be stated as a "younger state". But... There's "no gain without pain" for most people. This appears to essentially be a good way to move into better health by individuals with the proper "notion, and then motivation and discipline". In other words....."go into a FASTing state,...and letting the bodies do their' work to clean, rebuild other "sound cells", and move onto a higher state of functioning. Finally, this pathway,....totally understood or not....appears to be of major interest to all athletes,....individuals trying to lose weight...or just get "reset to a better health standing"...without drugs or medical intervention; the costs, toxic side effects,.....time waste, or arguments with other medical individuals who have a vested interest into "the economic realities of massive drug interventions that deal only with symtomologies alone...and do nothing to reset our cell function". Many drugs will become obsolete with this realization!
I studied Biochemistry in college. If anything, all those many classes I attended a decade ago had let me, now, enjoy and follow this wonderful discussion. Even without fancy editing or diagrams, Dr. Kroemer talking so eloquently in his German accent more than makes up for it. Thank you for sharing.
For those who need the subtitles: 1 - they can be dragged to the top of the video (click, hold, drag) 2 - add fun to the video checking out how many ways the CC tries to transcribe autophagy. Ayway, given is a non-native english speaker, the CC are pretty acurate. I'm try and getting back here to improve the caption on the "a topher G" misspell.
I found this interview extremely interesting, esp., about the importance of autophagy in using the immune system in the long term suppression of a cancer.
Thank you Dr. Rhonda and Dr. Guido. It was very rewarding experience in listening to this discussion. Additionally, the screen notes, slides, and time stamps greatly added to a greater understanding of the topics. I know the effort in producing such post discussion edits and addition of slides is huge effort. This does not go unnoticed and is greatly appreciated. It is unfortunate that other science discussions online do not employ nor engage the audience in such a professional and educational manner.
Excellent interview! Thank you. Have you re-interviewed Guido again since then, with more recent advances in his research? Thank you. Greetings fro Australis.
love it rhonda! the timeline is an amazing addition by the way, love how you can bounce back and fourth between topics and revisit those that you want to study more
Indeed a very enlightening explapnation of very complex subject. now I begin to understand why in some occasions we tend lose appetite or avoid foods when we are not well.
WOW! I mean... That was incredible! To have someone who knows the data so deeply and paired up with someone who knows all the right questions to ask. Even the point about coffee at the end, I thought "Dang, I only drink decaf, I wonder if it'll still be beneficial?" and then that data was given too. And all the information to cover the vocab as the video progressed, the sources and the diagrams! If schooling was taught like this, we'd all be geniuses by the time of high school graduation! I need more of this level of education. So informative, and useful and backed by science. Than you Rhonda! And thank you Dr. Guido Kroemer. This was amazing! I'll start to add some more of those things into my lifestyle; I'm currently on a prolonged fast and wanted to get more information about the benefits to keep me on track. I definitely need to make this a more regular part of my lifestyle!
26:20. Interesting you ask about the Exercise while Fasting. I have been doing 16 hour fasting and find it great for energy (Mental) and weight loss (Fat). Personally I find it really efficient to exercise at the 14th hour for about 30-45 minute run and then eat around the 15-16 hr to break the fast. I no longer have a 3pm low energy and have been loosing weight this way. :)
@@imanafdar Sort of. But It's more like 45 mins between cool down and meal. Start exercise at 12 finish just before 1, cool down. change, get food and then sit down and eat. So takes about 45 mins to cool down and get meal ready. By that time I'm hungry for nutrients haha Easier to have a healthy meal if you are hungry
I would love to see the next chapter of testing and trails for this study that have accumulated since this interview. Hopefully Dr. Rhonda Patrick can sit down with Dr. Guido soon 🙌🏾💙🙌🏾 thank you for this
It's fantastic and I couldn't be more thankful that you,special person, share with the whole community such infinitetly valuable informations. It's remarcable that you share whole interviews full of awesome infos,my deepest regards for all your work and for sharing it with us. I wish you all the best!
Rhonda, pls also consider recording a video on autophagy and virus infections. I have EBV virus, and available studies unfortunately show that fasting is not favourable in such environment
Interesting, he's also eating once a day - just like Dr. Nun Amen Ra who claims to strongly induce autophagy by fasting 23h every day. I'm on his regiment for about 3 months now, but only recently with caloric restriction and I do notice several positive effects.
She looks so beautiful and glowing. It is amazing she still has so much drive and energy to do this kind of interview while being pregnant. As a 22 yr old grad student in agronomy, I am so inspired by her to work harder and excel more in my field.
Fascinating and very important info! When protein management becomes dysregulated thanks to oxidative stress and insulin resistance you get everything from Kidney Stones to Alzheimers to Cataracts! A proper diet that's free of processed carbs should allow us to age much more gracefully with fewer complications.
You deserve that and more.... You bring life altering knowledge to people who would never gain access to it... I tell my family and friends about the topics you cover ..I send links..I get a sulforophane buzz every day. I sit in my sauna, I fast 3 to 4 days a week... You change peoples lives for the better...Good luck with the munchkin.
This was an amazing presentation!! It really helped connect the dots on how these mechanisms can dictate the outcomes in health and disease. I would certainly be interested in your thoughts on his personal regimen of prolonged fasting, exercise and diet. You are doing a great service to all of us.
Japanese scientiste Yoshinori Ohsumi has descovered the autophagy/self-eating or destruction, and he has obtained Nobel prize for that descovery which consist on how cells recycle their content.
There is a study clearly showing IF is having the same effect on lowering igf1 as 4 day continues fasting once a month . Another amazing inligtining interview , thank you so much.
Re3iRtH I don't have the link but I remember it was done by Dr Krista Varady and Dr Moseley tried this with the 5/2 fasting and got similar results. But there are many studies with similar results. The leading research into igf1 done by Dr Lango which has been on this channel as well in the past, michelsonmedical.org/2014/12/26/igf-1-fasting-discussion-valter-longo/
That said, what are you personally doing? I usually do a single 2-3 day fast per month and a 12:12 IF schedule. I think 16:8 wouldn't fit my schedule as I like a huge breakfast and function much better as a physician if I eat in the AM.. thanks
Yes, protein depletion has been tested on humans and protein deprivation has been practising for many years, but for the past 25 years in very large numbers at the sanatoriums of Dr Emilova in Bulgaria. Hundreds of thousands of people have been there fasting under doctors supervision and the data shows improving the health of all of them. You say here, we don't know. Yes, we do know. Its documented. And fasting could be done not only for more than 24 hours, but as long as 30 days eating fruits only. My own experience from it is also amazing. Of course fasting should always be done under doctors supervision as some conditions could get worse.
This is so fascinating!!! I'm definitely going to try to start a small fasting group with my friends to do 3 or 4 day fasts. Can't wait for more details to be researched. Mitochondrial biogenesis hollaaaaa
in her new book how to starve cancer jane maclland says autophagy can be a fuel for cancer and needs to be stopped as it acts as fuel for the cancer cell at certain periods of the process. The cancer cell uses autophagy when arginine is deprived it used glutimine
Tell me that intelligence isn’t cool. He’s brilliant and so is she…. She responds to each of his individual theses with a brief synopsis designed to punctuate what has been said she then asks a poignant question that is a progression of the thesis just discussed. This requires her to be operating on the same intellectual level as the guru himself and what about his vocabulary. Not a single throwaway word as he speaks in a language other than his first…. Incredible stuff!!!!
Hi Dr Patrick I was wondering what you think of the 'Snake Diet' which includes an intermittent fasting lifestyle. Is it safe to drink water with these ingredients while fasting? Will true autophagy occur? The creator of the diet says you lose too many electrolytes while fasting for longer periods like 48,72, or more hours. He says you need to replace lost salts and potassium while fasting or you will feel shaky. 'SNAKE JUICE' Water RECIPE Per 2 Liter H20: (Evian bottled water recommended because of PH) **drink less than 2L per day of the bottled water mixture** Potassium Chloride Powder = 2 tsp (4700 mg) ---(No Salt brand or Windsor salt free) Himalayan Pink Salt = 1 tsp (2,000 mg/L) Organic lemon Juice - 8 Tbs per day Organic apple cider vinegar - 4 Tbs per day
I'm going to start watching these videos with a notebook. God damn I love this channel! Thank you for making me smarter for free Dr Patrick, I and my family appreciate it very much.
@@IvanBFit and Lipzig - clearly you get how valuable Rhoda's efforts are. Please consider joining those of us on Patreon who don't get smarter here "for free", no one put in the effort or produces results like Dr. Patrick
personally from what i feel in my body, it takes about 18-24 hours with no food at all to ellicit autophagy, and thats just when it starts. i can "feel" my body burning its fat and i become mentally 'sharper" usually around 18-20hours or so with no food and it kicks in. So my feeling is that we should fast for 24-36hours on a regular basis (twice a week or so) to reap fantastic health benefits and thats what ive been doing lately. ive lost 50lbs (doing this off and on for a few months) and i feel much better and sleep better and my anxiety issues have gone 99% away ! basically look at it realistically, if you eat a big meal , it stays in stomach 3-8hours or so depending on the crap you ate lol, hell sometimes up too 12hours.... then it has to go through 20 feet of your intestines! so if you dont eat in 18hours or so, thats not that big a deal! wtf, your good for 36-48+ hours really. Not like your gonna starve... Give your body a chance to heal itself (Autophagy) Screw eating every 2-3hours, thats BS....I find Dr Rhonda and her vids very fascinating and informative! She is totally right about all this and i love really finding out how it all works in the microscopic level, very interesting ! Well Done Rhonda =)
Robert222 Lewis yeah I'm not so certain about that approach. There are more questions than answers about it quite frankly and I think we're kind of overselling fasting. Nothing really comes caveat free. Fasting is great, but if someone wants to exercise the 48-hr weekly fasting not so good of an idea. And avoiding food in that manner to me is an extreme way to deal with food intake. I say eat every 3-6 or more hours. 3 minimum, 4-5 ideal. And yes fast from time to time or simply IF. Exercise stimulates autophagy and so does simply.eating plant-based and under caloric restriction.
Amazing interview!! Touched on so many subjects and questions about autophagy in regards to intermittent fasting. Blown away by the details and I look forward to the progress of this amazing subject.
I would love to know his (or Rhonda’s) opinion on the optimal extended fast to maximize autophagy?? 5 days seems to be the consensus among experts, but as it’s not measurable isn’t that speculative. I see no reason why 7 days isn’t “better” for most or at least many people. particularly this with immune system issues ? . Thanks again. Guido’s awesome! Thrilled about his coffee comments!
Dr Longo suggests that fasting longer than 5 days might send the body into a thrifty mode, where it slows down the metabolism more than desirable, although I have never seen him present the evidence for the rationale
Question what percentage of those that were starved ie held in captivity during wars lived to super centenarian age? Large populations have been starved in different periods in our history surely studying their lifespans would shed light on whether repeated dating is good for the body
Nicely done, even though most has gone over my uneducated head love how you add illustration and definitions et al.Having to educate myself having been recently diagnosed with cll and given NO advice on exercise, diet,just wait and see is the standard. Keep up your good work.Thanx
SOME OF HABITS OF FASTING OR SEMIFASTING IS TO BE DEVELOPED SINCE CHILDHOOD SO BECOMES AHABIT WHEN YOU GET OLDER .IM INDIA A BRANCH NAMESD JAINS ARE TRAINED TO INTERMITTENT FASTING { ALMOST 1WEEK { FROM AGE OF 12 OR SO
8:45 - so, as someone with T1 diabetes, every time I have a low blood sugar, I'm depriving my cells of glucose and therefore accelerating autophagy? If that's correct, then that's just one more depressing ballache about this disease =(
So much info here!! Each time stamp could be expanded into another stand alone video series. I have to say, I still cringe every time people use the phrase “caloric restriction” as if all calories (wether fat or carbohydrates) metabolize to energy the same. They’re assuming humans and animals are calorimeters. Also, far too many researchers incorrectly assume that ketogenesis is not a normal state of human metabolism and that ketones cannot be our primary source of energy. Let’s at least be sure to correct researchers who claim that a low carb diet is up to 20% of calories from carbohydrate when in fact a low carb diet should be closer to 5% or at least low enough to encourage lipolysis and maintenance of a low level of serum ketones.
I wish that in English we had one word for emotional stress and a separate word for physical stress. It can be muddy using the word in both capacities.
49:00 then why do they always tell people on chemo to eat a lot of food while in therapy? To me it sounds like, from this information shared here, that fasting during chemo therapy can be beneficial.
TIMELINE...
• 00:03:22 - How genetically inhibiting autophagy actually increases cellular sensitivity to death and how this was counterintuitive because autophagy was thought, at one time, as a type of activity predominantly concerned with actually initiating cell death.
• 00:04:44 - The external signals causing autophagy.
• 00:05:29 - The role of growth factors in transporting nutrients from the outside world into the intracellular space.
• 00:05:48 - Autophagy as a process that destroys bioenergetic macromolecular reserves including proteins, lipids, and nucleic acids to generate energy.
• 00:06:28 - How declines in the ATP (energetic) status of the cell trigger autophagy by increasing the activity of a pathway known as AMP Kinase.
• 00:06:36 - How reductions in the cytosolic pool of acetyl-CoA as a consequence of reductions in glycolysis, amino acid catabolism, or beta-oxidation, ultimately result in the de-acetylation of hundreds of cellular proteins involved in autophagy. Nutrient deprivation → ↑ Protein Deacetylation (↓ cytosolic Acetyl CoA) + ↓ mTOR + ↑ AMP Kinase → Autophagy
• 00:09:37 - The role of the inhibition of mTOR and activation of AMP Kinase in cellular autophagy. mTOR is a pathway robustly activated by IGF-1 and associated with increases in cell growth, proliferation, motility and protein synthesis. AMP Kinase, on the other hand, is a pathway important in regulating cellular energy homeostasis by inhibiting synthesis of fatty acids and triglycerides and activating fatty acid uptake and beta-oxidation in the liver.
• 00:09:37 - The indirect relationship between protein acetylation status (and cytosolic acetyl CoA availability) and the suppression of mTOR and activation of AMP Kinase in cellular autophagy.
• 00:10:23 - The possibility of using selective nutrient restriction as an autophagy-inducer instead of more generalized nutrient deprivation or fasting.
• 00:11:11 - Cytoplasmic protein deacetylation as a potential surrogate marker for fasting-induced autophagy (still undergoing validation) but possibly not other forms of autophagy, such as the kind pharmacologically induced by interaction with a protein involved in vesicle-trafficking processes called Beclin 1.
• 00:12:53 - How a protein called LC3 associate with structures called autophagosomes to facilitate autophagy in response to deacetylation it undergoes. Note: this sirt1-mediated deacetylation of LC3 is induced as an important response to cell starvation.
• 00:14:22 - The special flow cytometry needed in order to measure some of the proteins associated with the activation of autophagosomes in autophagy.
• 00:15:04 - The desirability of being able to know and test whether or not your fasting is triggering robust autophagy or not.
• 00:16:30 - The minimum amount of fasting necessary to activate autophagy.
• 00:16:56 - Whether or not time-restricted eating or 16:8 intermittent fasting reliably induces autophagy in any of our tissues.
• 00:17:57 - The important differences between prolonged fasting in humans and the rodent animal models used in studies.
• 00:19:03 - The ~12-hour half-life of IGF-1 and whether or not that has any implications for the potential of autophagy in shorter duration fasts.
• 00:20:12 - The effects of long-term caloric restriction on markers of cellular autophagy in humans.
• 00:21:32 - The effect of an every-other-day eating pattern in rodents and how this pattern actually mimics the longevity producing effects of caloric restriction but with the advantage of stabilizing long-term at a more normal body weight. (Note: Dr. Kroemer is quick to point out that this type of intermittent fasting is more dramatic than it would be in humans because of differences in metabolism… the animals actually experience a 10% oscillation in body weight from this pattern!)
• 00:24:35 - The effect of exercise (especially endurance exercise) on autophagy in muscle tissue.
• 00:25:08 - The role of autophagy as a mediator of the anti-obesity and anti-diabetic effects of endurance exercise.
• 00:26:58 - The differences between macroautophagy, microautophagy, and chaperone-mediated autophagy.
• 00:28:03 - The difference between autophagy that is dictated by demand (nutrient stress) versus autophagy that occurs as the need arises to recycle damaged organelles.
• 00:28:40 - How damaged organelles change the composition of their surfaces in order to decorate them with signals for the stimulation of their engulfment by the autophagosome.
• 00:29:07 - The many, many names autophagy has when we are talking about it in the context of specific macromolecular structures and organelles (e.g. mitophagy for mitochondria, pexophagy for peroxisomes, reticulophagy for endoplasmic reticulum, ribophagy for ribosomes, and virophagy for viruses).
• 00:29:35 - How autophagy from nutrient deprivation still prefers to first recycle organelles that have been slightly marked… in other words, that are already aged or slightly damaged.
• 00:31:15 - How mitochondrial use ubiquitination, a process which occurs when these organelles begin to lose their membrane potential, in order to signal damage and to ensure preferential targeting by the autophagic machinery. ↓ mitochondrial transmembrane potential → ↑ ubiquitination → ↑ mitophagy
• 00:32:42 - The coordinated manner in which mitophagy and mitochondrial biogenesis act together in a closed feedback loop in order to preserve mitochondrial quality while preserving the total pool of functioning mitochondria.
• 00:33:34 - The changes that can occur in total mitochondrial pool as cells adapt to take on new metabolic profiles through a mitophagy-mediated process. This can occur as cells differentiate into new cell types that are specialized for glycolytic energy generation.
• 00:35:13 - The role autophagy plays in the prevention of neurodegenerative diseases caused by protein aggregates.
• 00:37:18 - How autosomal recessive mutations (where both parents must contribute a defective gene for PD to arise in the offspring) in a kinase protein called PINK1 disrupts its ability to recruit a protein called Parkin that mediates the targeting of mitochondria for mitophagy. ↓ PINK1’s kinase activity → ↓ parkin recruitment → ↓ mitophagy → ↑ accumulation of damaged mitochondria
• 00:38:01 - Mitochondrial membrane permeabilization as a death signal due to the release of dangerous proteins contained in the mitochondria.
• 00:39:05 - Dr. Valter Longo’s research demonstrating a cycle of prolonged fasting followed by a refeeding can recycle 28% of the white blood cells, and reduce the severity of an autoimmune disease (multiple sclerosis).
• 00:39:52 - The evolutionarily-conserved sickness response (food avoidance) as a way of beneficially altering immune responses through through altered metabolism and autophagy.
• 00:41:02 - The surprising increase in lethality that happens when mice are force fed (glucose in this case) while exhibiting sickness response from a bacterial challenge.
• 00:42:27 - The effects of an anti-malarial known as chloroquine which has some cytotoxic effects in cancer cells, but is actually (surprisingly) an inhibitor of autophagy.
• 00:43:12 - Studies of the lysosomal disrupter and anti-malarial chloroquine in combination with chemotherapy in the treatment of cancer.
• 00:44:04 - The differential roles autophagy plays in the progression of cancer in pre-malignant cells, when it is suppressed, versus in malignant cells, when it is sometimes used as an adaptation helpful to the survival of malignant cells experiencing environmental stress. ↓ tumor suppressor gene activity → ↓ autophagy → survival of pre-malignant cells → ↑ autophagy as a malignant adaptation
• 00:44:49 - How inhibition of autophagy by itself is sufficient to induce oncogenesis, particularly in leukemia.
• 00:48:10 - How cells undergoing autophagy can release ATP into the extracellular space where it can function as a signal that recruits and activates immune cells against tumor antigens through the activities of purinergic receptors. ↑ autophagy → ↑ extracellular ATP → activation of purinergic receptor-mediated immunosurveillance
• 00:48:49 - The importance of the triggering of this immunosurveilance system as part of the cell death associated with chemotherapy.
• 00:50:27 - The class of compounds known as “caloric restriction mimetics” that affect autophagy by perturbing various pathways in such a way as to reductions in cytosolic acetyl CoA and protein deacetylation in a manner similar to nutrient deprivation. Examples include: hydroxycitrate (inhibits ATP citrate lyase), spermidine (inhibits Ep300, a protein acetyltransferase), and resveratrol (activates deacetylases).
• 00:55:27 - How intestinal bacteria may produce as much as 1/3rd of the body’s spermidine and how this production rate can be manipulated by probiotic and dietary interventions.
• 00:56:17 - How the ability of caloric restriction mimetics (CRMs) to induce a type of autophagy that provokes immunosurveillance potentially offers an opportunity for synergy when used in combination with chemotherapeutic agents in the treatment of cancer.
• 00:56:56 - How the inhibition of autophagy in malignant cells or destruction of the extracellular ATP released by cells undergoing autophagy is able to abolish the favorable interaction between caloric restriction mimetic drugs and chemotherapy.
• 00:58:02 - The tendency for dietary consumption of caloric restriction mimetics, particularly hydroxy citrate, to induce autophagy and reduce weight gain in mice fed an obesogenic diet.
• 00:59:17 - Dr. Kroemer’s personal intermittent and prolonged fasting practices and his habit of consuming foods that may contain some natural quantities of caloric restriction mimicking compounds.
• 01:01:40 - The autophagy-enhancing effect of coffee (with and without caffeine).
Te amount of info and passion you put in your videos it's increbile but this comment/timing
is above increbile.
Trinitrophenylnitramine It's complicated. But RT has been found to actually stimulate autophagy if I'm not mistaken. in fact I just Googled resistance training and autophagy and a few studies came up instantly showing how resistance training stimulates autophagy and how autophagy plays a role in the performance and training adaptations. I like to think of it this way yes resistance training increases igf-1, but I think it may be dose-dependent. And if you think about it resistance training initially is catabolic because it breaks down muscle tissue and then when we recover, it rebuilds. Endurance exercise definitely stimulates autophagy.
27:04 on the possible synergy between fasting and exercise: the paper your cited just before www.researchgate.net/publication/276066849_Activation_of_autophagy_in_human_skeletal_muscle_is_dependent_on_exercise_intensity_and_AMPK_activation seems to examine exactly that. It showed that intensity of concentric exercise more than feeding state is correlated to autophagy. If I understand the paper correctly.
FoundMyFitness Dr. Patrick..
Do you think autophagy will also consume THC metabolites and allow rapid THC detox for people who have smoked pot?
The problem THC metabolites are fat soluble and store themselves in fat for to be slowly detoxed over time.
That’s really cool of you to break this down for us. It helps when you go back.
I consider myself very fortunate to be living in an age when this type of information is so readily available to the common man.
Amazing that the sum total of human knowledge and the latest research is at our fingertips. Still, people need to make the effort to be their own best advocates for their health instead of medical industry shills that put profits before people.
This knowledge has been around for centuries! lol But people don't like 'popular wisdom' and think science figures things out... Which yeah is an healthy way to have about things... Because it's better to have prove than just words... But the non laboratory scientists are not that dumb. They have a sense of what's going on. Even religion has a commandment for gluttony for example. So 2000 years ago they're already talking about this at least!
And now we're hungry, lets eat!
@@JohnSmith-um4tv 😊😊😊
And yet so many stupid people still around that believe God cursed all of His Creation to dreadful pain and excruciating suffering just because one guy ate a piece of fruit thousands of years ago!
How intelligent is this guy! Wow, a knockout interview. Also, I can tell you took the time to edit the closed captioning, which isn't easy or quick. Wanted to express my appreciation for that, because having captions on helps me concentrate and retain information. Thank you for producing all these high quality, informative videos.
Thank you for the nice note! The whole transcript is also posted on the episode page on the website at foundmyfitness.com/episodes/guido-kroemer.
Moreover, they're searchable at foundmyfitness.com/search.
Amen
@@FoundMyFitness I TOTALLY CONCUR with Tyanite about the benefit of the closed captions, without which I CANNOT watch this, or any other, vid, 'cause I'm nearly deaf.
The fact that the auto-generated captions being edited is a huge WOW for me; and on top of that, there' is a freak'n TRANSCRIPT of this vid!
It does not get better than this for deaf people!
THANK YOU SO MUCH, Rhonda! You are a true HERO to many!
I really appreciate your interview technique - you let the guest talk, and then summarize and help expand the guest's points. Thank you!
Bravo to you and her!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
Rare to find a raw , unfiltered podcast that focuses on the science , without dumbing it down to pander to the audience. I didn't understand a lot of the cellular mechanisms entirely , but the numerous papers being cited, motivate me enough to find out. Dr Guido seems like on of the most knowledgeable persons I've seen on your podcast, its impressive to hear the breadth of his knowledge.
P.S Spermidine in cheese in synergy with resveratrol in wine , would be interesting to see if this is a reason behind the French longevity paradox.
I agree with you, just keep in mind that to intelligently decide what you believe you need to have an understanding of research. You need to decide for yourself whether or not you believe the studies cited truly prove the speakers point and how strongly. Personally I remain skeptical in most cases even if I am convinced enough to apply what someone is saying.
Fantastic interview, even more remarkable when you think that English is the second language from Dr Kroemer! He speaks better English than most of us native speakers.
I find that the people with the most knowledge and intelligence are very calm and don't let their emotions get involved with their answers.
I didn't understand everything he was talking about but bit by bit, I am getting very interested in fasting and autophagy. When a man like Dr.Kroemer is on OMAD plus prolonged fasting, not to mention wine and cheese! That is good enough for me
Thanks and keep them coming!
That baby is gonna be immortal
LOLOL Jerry
I think I see it glowing from here
lol yeah
Jerry, Moostache, you are not trying to be funny, are you?
he is serious @@rogerbird5665
Top 10, or even 5 here Rhonda, this was an exceptional interview! There is beauty in science, you know how to waltz with intellects and match them step for step. There were so many "connect the dots" moments for me in this one, I'm sharing it far and wide, and coming back for the encore. Bravo, and many thanks to Guido for coming on, he clearly appreciated your considerate, intelligent interview style. So grateful for your work, thank you.
If you watched this video, you qualify for 3 College credit hours.
Dude, defiently. The interviewee is even slowing his speaking patterns and it's still difficult to follow.
Yes. You get a P for participation and a gold star if you seem particularly interested.
People who attend Trump rallies think that Dr Fauci speaks in a high scientific register. No, he does not. _This_ is the full meal deal and I'm loving every minute.
Thank you, and that while painting my room 😀
Nice job Dr. Patrick, your videos are getting better and better :) The extra multimedia inserts make these things so much easier to understand for the rest of us.
The way Dr. Kroemer pronounces autophagy is borderline ASMR. I could listen to 9 more hours of this.
This was an excellent episode. What a brilliant mind, and a superb moderator/scientist asking all the right questions. Fascinating!
My thinking is that Dr. Patrick is pretty humble.
I feel fortunate every time I watch one of her videos
on whatever subject I have ‘searched out.’
She’s like a modern-day Leonardo DV that we
get to watch on you.tube🇺🇸
Great video! Have been following you since I came across your lecture on hypothermic conditioning and epigenetic mechanisms. You have a great way of expressing information so it's easily understood. I have put your science into practice and have seen tremendous results at 39. Eating 1 meal a day for 7 months I've lost 45lbs and gained a whopping 18lbs of lean muscle mass. After around 18hrs my t levels and igf-1 literally go through the roof so it feels. I hope you read this because I really want express my gratitude for your work and helping people. Great work Dr Patrick!
This guy is the real deal. He's got 'skills to pay the bills'.
You know it like a poet! :)
The quality of information and how it's presented is ridiculously good! I'm learning more here than in my Cellular biology class at University.
This is one of the best interviews I've seen on this channel! Super comprehensive!!!!
Thank you so much! So much time you must have spent putting all of this together. Pro tip:I watch this on my phone and tablet at the same time so I can pause the pictures and articles. Probably because I’m slow and need more autophagy in my life.
I had such bad breakouts (often around my chin, jawline, neck) as my hormones began changing in my 40's. It was so aggravating, but things leveled out and my skin is usually clear now! Just in time for deeper wrinkles and sagging...😅
You're so young and gorgeous! I can't wait to try these techniques!❤
Wow ..that was an amazing interview. I think I'm going to have to listen a few more times to absorb all this great information.
Huge thanks for you and your team offering the non-academic interested audience the latest progress on research, and these amazing illustration is pulling us to keep up, This channel offers one of the most professional and responsible content in this field; big thanks and respect
Really appreciate the time you take to create the helpful diagrams/definitions in the video. Ive only done 2 semester of biochem so far hehe
You are very welcome =)
This became my favorite youtube channel in less than 24h, the best ever! Big hello from East Europe!
Hello and thank you, Lela!
Hello from Timişoara
I love how this gives me so much information. How great it is to be living in a time with this much information out there and the difference between of opinions on this subject. It’s great!!!
Like at least one other commenter, down below, I fast 15 - 16 hours every day. My morning workout comes just before breakfast. Except, I've been doing this four years. I'm almost never hungry, no matter what time of day, and at 67, I don't have much gray hair (which is said to be caused by senescent cells around the hair follicles). As Dr. Ohsumi said in one of his lectures, during complete cellular autophagy, about half the cells consumed are healthy and about half are unhealthy (usually senescent). And as we all believe we know, senescent cells are the bad guys. The body keeps cells around that it would normally kill and eat. But if the body isn't hungry, it keeps these for a snack "later." Very often, "later" never arrives.
I don't like working out after a meal, so I work out in the mornings, before breakfast, when my stomach is fairly down to empty. I always have tons of energy and more to spare.
I'm also deeply engaged in a ketogenic diet (low carb, low protein, high fat). I'm surprised, over the last four years, that the more fat in my diet, the more weight I've lost. It also appears that, if you don't give your body enough energy to function, it will break down protein and turn it, essentially, into carbs.
One day recently, after a bike ride, a friend pulled out some meaty treats (slim jim style - I said they look like doggie treats) and offered me some. I mansplained this to her and said, "you may as well be eating potato chips." She said, "Nu uh." I said, "Uh huh." And that went on a few rounds.
But we know that carb burners need energy every two hours or they get hungry. Fat-adapted folk can go for a fairly long while (days, weeks, months) without food, and never get hungry. At the end of a 16 hour fast, you're burning fat (there are no carbs left in your stomach to burn).
My most recent blood tests were pretty amazing, so I'm fairly enamored of this diet. I'm always eating the tastiest, fattest, richest, saltiest delicious diet imaginable (I use potassium-sodium 50-50 salt), with almost no carbs, and somewhat low protein.
I only eat two meals a day and they're fairly small. I can't seem to fit a third meal (lunch) in. It's just breakfast and dinner.
I would like to offer my sincere thanks for this incredible information. It was so interesting to listen to and extremely helpful. I am going to start implementing 3 days water fasts every month for the autophagy benefits now!!
So....we now know...that beyond the Lysosome...that we've known about for 30 years...that we have an endometabolic mechanism to "clean ourselves out; intracellularly for our recapturing of said proteins/amino acids for the resequestering of our own reuse.
This explains alot,....as related to our ability to fast for many days, weeks,...and even months when "food" is not available..or for our own 'desire' to readapt our inherent cellular mechanism back what may be stated as a "younger state". But...
There's "no gain without pain" for most people. This appears to essentially be a good way to move into better health by individuals with the proper "notion, and then motivation and discipline". In other words....."go into a FASTing state,...and letting the bodies do their' work to clean, rebuild other "sound cells", and move onto a higher state of functioning.
Finally, this pathway,....totally understood or not....appears to be of major interest to all athletes,....individuals trying to lose weight...or just get "reset to a better health standing"...without drugs or medical intervention; the costs, toxic side effects,.....time waste, or arguments with other medical individuals who have a vested interest into "the economic realities of massive drug interventions that deal only with symtomologies alone...and do nothing to reset our cell function".
Many drugs will become obsolete with this realization!
wow this guy is excellent. thank you so much for interviewing him!!
I studied Biochemistry in college. If anything, all those many classes I attended a decade ago had let me, now, enjoy and follow this wonderful discussion. Even without fancy editing or diagrams, Dr. Kroemer talking so eloquently in his German accent more than makes up for it. Thank you for sharing.
Wonderful interview for improving one’s health and slow aging. Thanks very much.
For those who need the subtitles:
1 - they can be dragged to the top of the video (click, hold, drag)
2 - add fun to the video checking out how many ways the CC tries to transcribe autophagy. Ayway, given is a non-native english speaker, the CC are pretty acurate. I'm try and getting back here to improve the caption on the "a topher G" misspell.
Autophagy is not an english word
Another excellent interview, Dr. Patrick. You maximized this opportunity! Thanks so much to both Docs, and soon I'll be supporting at Patreon.
Thank you both..I could not stop watching. Very enlightening
Dr.Patrick is one of the best interviewers. Fantastic information. Keep up the good work!
I found this interview extremely interesting, esp., about the importance of autophagy in using the immune system in the long term suppression of a cancer.
Congratulations on your pregnancy!! wish you all the best!!
Thank you Dr. Rhonda and Dr. Guido. It was very rewarding experience in listening to this discussion. Additionally, the screen notes, slides, and time stamps greatly added to a greater understanding of the topics. I know the effort in producing such post discussion edits and addition of slides is huge effort. This does not go unnoticed and is greatly appreciated. It is unfortunate that other science discussions online do not employ nor engage the audience in such a professional and educational manner.
Excellent interview! Thank you. Have you re-interviewed Guido again since then, with more recent advances in his research? Thank you. Greetings fro Australis.
love it rhonda! the timeline is an amazing addition by the way, love how you can bounce back and fourth between topics and revisit those that you want to study more
This is the best page I’ve ever discovered
Indeed a very enlightening explapnation of very complex subject. now I begin to understand why in some occasions we tend lose appetite or avoid foods when we are not well.
WOW! I mean... That was incredible!
To have someone who knows the data so deeply and paired up with someone who knows all the right questions to ask. Even the point about coffee at the end, I thought "Dang, I only drink decaf, I wonder if it'll still be beneficial?" and then that data was given too.
And all the information to cover the vocab as the video progressed, the sources and the diagrams!
If schooling was taught like this, we'd all be geniuses by the time of high school graduation!
I need more of this level of education. So informative, and useful and backed by science.
Than you Rhonda! And thank you Dr. Guido Kroemer.
This was amazing!
I'll start to add some more of those things into my lifestyle; I'm currently on a prolonged fast and wanted to get more information about the benefits to keep me on track. I definitely need to make this a more regular part of my lifestyle!
26:20. Interesting you ask about the Exercise while Fasting. I have been doing 16 hour fasting and find it great for energy (Mental) and weight loss (Fat). Personally I find it really efficient to exercise at the 14th hour for about 30-45 minute run and then eat around the 15-16 hr to break the fast. I no longer have a 3pm low energy and have been loosing weight this way. :)
So you exercise 2 hours before you break your fast?
@@imanafdar Sort of. But It's more like 45 mins between cool down and meal. Start exercise at 12 finish just before 1, cool down. change, get food and then sit down and eat. So takes about 45 mins to cool down and get meal ready. By that time I'm hungry for nutrients haha Easier to have a healthy meal if you are hungry
Do you know how healthy this baby is going to be with a mom like her? It's going to be in a sauna In no time!
In a way, it's already in a 98.6 degree sauna.
Appreciate this great video from two wonderful people.
I would love to see the next chapter of testing and trails for this study that have accumulated since this interview. Hopefully Dr. Rhonda Patrick can sit down with Dr. Guido soon 🙌🏾💙🙌🏾 thank you for this
It's fantastic and I couldn't be more thankful that you,special person, share with the whole community such infinitetly valuable informations. It's remarcable that you share whole interviews full of awesome infos,my deepest regards for all your work and for sharing it with us. I wish you all the best!
Rhonda, pls also consider recording a video on autophagy and virus infections. I have EBV virus, and available studies unfortunately show that fasting is not favourable in such environment
How lucky are we man. great interview
Interesting, he's also eating once a day - just like Dr. Nun Amen Ra who claims to strongly induce autophagy by fasting 23h every day. I'm on his regiment for about 3 months now, but only recently with caloric restriction and I do notice several positive effects.
Awesome interview as usual Rhonda. I’ve been a huge Valter Longo fan for about 7 years and Guido is the only expert I would put in his leaug
Me too
She looks so beautiful and glowing. It is amazing she still has so much drive and energy to do this kind of interview while being pregnant. As a 22 yr old grad student in agronomy, I am so inspired by her to work harder and excel more in my field.
Definitely watching this when I get out of work. Thank you Dr. Rhonda!!!
Fascinating and very important info! When protein management becomes dysregulated thanks to oxidative stress and insulin resistance you get everything from Kidney Stones to Alzheimers to Cataracts! A proper diet that's free of processed carbs should allow us to age much more gracefully with fewer complications.
I would to shore our discoveries a Cancer Survivor !
You're really knockin us out with these videos... It's exciting and I'm grateful that you post them. Thank you
Thanks for the encouragement, David!
You deserve that and more.... You bring life altering knowledge to people who would never gain access to it... I tell my family and friends about the topics you cover ..I send links..I get a sulforophane buzz every day. I sit in my sauna, I fast 3 to 4 days a week... You change peoples lives for the better...Good luck with the munchkin.
This was an amazing presentation!! It really helped connect the dots on how these mechanisms can dictate the outcomes in health and disease. I would certainly be interested in your thoughts on his personal regimen of prolonged fasting, exercise and diet. You are doing a great service to all of us.
I don't even consider a 14 hour fast mentionable as a fast.
Real smooth way of asking Rhonda out for a drink doc!
How can this possibly so interesting that I don't want to even pause it?
Japanese scientiste Yoshinori Ohsumi has descovered the autophagy/self-eating or destruction, and he has obtained Nobel prize for that descovery which consist on how cells recycle their content.
The on-screen footnotes are a nice touch.
There is a study clearly showing IF is having the same effect on lowering igf1 as 4 day continues fasting once a month . Another amazing inligtining interview , thank you so much.
supernova1976 I just did a very research based video on IGF-1 and reference Dr. Patrick's video.
Do you have link for that study? cheers
Re3iRtH I don't have the link but I remember it was done by Dr Krista Varady and Dr Moseley tried this with the 5/2 fasting and got similar results. But there are many studies with similar results. The leading research into igf1 done by Dr Lango which has been on this channel as well in the past, michelsonmedical.org/2014/12/26/igf-1-fasting-discussion-valter-longo/
That said, what are you personally doing? I usually do a single 2-3 day fast per month and a 12:12 IF schedule. I think 16:8 wouldn't fit my schedule as I like a huge breakfast and function much better as a physician if I eat in the AM.. thanks
I respectfully call bullshit! Please link documentation
This man is a wizard.
Yes, protein depletion has been tested on humans and protein deprivation has been practising for many years, but for the past 25 years in very large numbers at the sanatoriums of Dr Emilova in Bulgaria. Hundreds of thousands of people have been there fasting under doctors supervision and the data shows improving the health of all of them. You say here, we don't know. Yes, we do know. Its documented. And fasting could be done not only for more than 24 hours, but as long as 30 days eating fruits only. My own experience from it is also amazing. Of course fasting should always be done under doctors supervision as some conditions could get worse.
So it takes a minimum of 3 days of fasting before a meaningful level autophagy is activated. Interesting!
It takes between 2 to 4 days, depending on your physical fitness.
Amazing! I started it over right after it finished playing. Thanks Dr. Patrick
This is so fascinating!!! I'm definitely going to try to start a small fasting group with my friends to do 3 or 4 day fasts. Can't wait for more details to be researched. Mitochondrial biogenesis hollaaaaa
in her new book how to starve cancer jane maclland says autophagy can be a fuel for cancer and needs to be stopped as it acts as fuel for the cancer cell at certain periods of the process. The cancer cell uses autophagy when arginine is deprived it used glutimine
This is just brilliant.
Tell me that intelligence isn’t cool. He’s brilliant and so is she….
She responds to each of his individual theses with a brief synopsis designed to punctuate what has been said she then asks a poignant question that is a progression of the thesis just discussed. This requires her to be operating on the same intellectual level as the guru himself and what about his vocabulary. Not a single throwaway word as he speaks in a language other than his first….
Incredible stuff!!!!
wow thanks for writing down the biology terms as he was describing this stuff, I really do appreciate that very helpful!
Hi Dr Patrick
I was wondering what you think of the 'Snake Diet' which includes an intermittent fasting lifestyle. Is it safe to drink water with these ingredients while fasting? Will true autophagy occur? The creator of the diet says you lose too many electrolytes while fasting for longer periods like 48,72, or more hours. He says you need to replace lost salts and potassium while fasting or you will feel shaky.
'SNAKE JUICE' Water RECIPE
Per 2 Liter H20:
(Evian bottled water recommended because of PH)
**drink less than 2L per day of the bottled water mixture**
Potassium Chloride Powder = 2 tsp
(4700 mg) ---(No Salt brand or Windsor salt free)
Himalayan Pink Salt = 1 tsp
(2,000 mg/L)
Organic lemon Juice - 8 Tbs per day
Organic apple cider vinegar - 4 Tbs per day
Went from 340 to 223 following Coles protocol
I'm going to start watching these videos with a notebook. God damn I love this channel! Thank you for making me smarter for free Dr Patrick, I and my family appreciate it very much.
Lipzig Schweitzer I echo your appreciation. She is so amazing.
@@IvanBFit and Lipzig - clearly you get how valuable Rhoda's efforts are. Please consider joining those of us on Patreon who don't get smarter here "for free", no one put in the effort or produces results like Dr. Patrick
I listen to _all_ my videos with my electronic notebook open, and I simply gave up on the first pass, there's too much to capture.
spermadine found in sperm is a great anti aging treatment! I've got to get my wife to buy into this!
Congratulations on the baby! You look beautiful.
Beautifully swollen up.
thankyou!
His accent automatically gives him more credibility. Great interview!
Lol
Not his accent, but rather the knowledge, serenity and mastering of the topic
personally from what i feel in my body, it takes about 18-24 hours with no food at all to ellicit autophagy, and thats just when it starts. i can "feel" my body burning its fat and i become mentally 'sharper" usually around 18-20hours or so with no food and it kicks in. So my feeling is that we should fast for 24-36hours on a regular basis (twice a week or so) to reap fantastic health benefits and thats what ive been doing lately. ive lost 50lbs (doing this off and on for a few months) and i feel much better and sleep better and my anxiety issues have gone 99% away ! basically look at it realistically, if you eat a big meal , it stays in stomach 3-8hours or so depending on the crap you ate lol, hell sometimes up too 12hours.... then it has to go through 20 feet of your intestines! so if you dont eat in 18hours or so, thats not that big a deal! wtf, your good for 36-48+ hours really. Not like your gonna starve... Give your body a chance to heal itself (Autophagy) Screw eating every 2-3hours, thats BS....I find Dr Rhonda and her vids very fascinating and informative! She is totally right about all this and i love really finding out how it all works in the microscopic level, very interesting ! Well Done Rhonda =)
Robert222 Lewis yeah I'm not so certain about that approach. There are more questions than answers about it quite frankly and I think we're kind of overselling fasting. Nothing really comes caveat free. Fasting is great, but if someone wants to exercise the 48-hr weekly fasting not so good of an idea. And avoiding food in that manner to me is an extreme way to deal with food intake. I say eat every 3-6 or more hours. 3 minimum, 4-5 ideal. And yes fast from time to time or simply IF. Exercise stimulates autophagy and so does simply.eating plant-based and under caloric restriction.
@@IvanBFit how exactly is eating every 4 hours consistent with IF? Your post is contradictory. 🙄
Amazing interview!! Touched on so many subjects and questions about autophagy in regards to intermittent fasting. Blown away by the details and I look forward to the progress of this amazing subject.
What an awesome guy. I gotta start drinking coffee now.
Dr Patrick, we would still LOVE for you to interview Dr Carolyn on magnesium! An hour talk with you two on magnesium... would juss be awesome!
LOL Hello fellow food geek!
I would love to hear his vision about the effectiveness of dry-fasting
I would love to know his (or Rhonda’s) opinion on the optimal extended fast to maximize autophagy?? 5 days seems to be the consensus among experts, but as it’s not measurable isn’t that speculative. I see no reason why 7 days isn’t “better” for most or at least many people. particularly this with immune system issues ? . Thanks again. Guido’s awesome! Thrilled about his coffee comments!
Dr Longo suggests that fasting longer than 5 days might send the body into a thrifty mode, where it slows down the metabolism more than desirable, although I have never seen him present the evidence for the rationale
Studies have shown that excessive Autophagy may kill cells in the Heart. Scientists have linked excessive Autophagy to some Heart problems.
Question what percentage of those that were starved ie held in captivity during wars lived to super centenarian age? Large populations have been starved in different periods in our history surely studying their lifespans would shed light on whether repeated dating is good for the body
You're looking well! The world needs the info you help share, tyvm for your efforts!
Only at 25:55 he got the first opportunity to get a glimpse at Rhonda's legs AND HE TOOK IT! What a tough man he fought it half an hour 😊
This is wonderfully done Thank you Dr. Rhonda you’re amazing!
Thank you for all you are doing, DRP! This stuff is SUPER IMPORTANT. I've been listening to a good bit from Dr. Thomas Seyfried as of late, too.
Nicely done, even though most has gone over my uneducated head love how you add illustration and definitions et al.Having to educate myself having been recently diagnosed with cll and given NO advice on exercise, diet,just wait and see is the standard. Keep up your good work.Thanx
This guy knows his stuff
Studies have shown that excessive Autophagy may kill cells in the Heart. Scientists have linked excessive Autophagy to some Heart problems.
Great interview, thank you both!
This is fantastic information thank you so much for making all this knowledge so easily available!
Very interesting talk, thank you.
SOME OF HABITS OF FASTING OR SEMIFASTING IS TO BE DEVELOPED SINCE CHILDHOOD SO BECOMES AHABIT WHEN YOU GET OLDER .IM INDIA A BRANCH NAMESD JAINS ARE TRAINED TO INTERMITTENT FASTING { ALMOST 1WEEK { FROM AGE OF 12 OR SO
8:45 - so, as someone with T1 diabetes, every time I have a low blood sugar, I'm depriving my cells of glucose and therefore accelerating autophagy? If that's correct, then that's just one more depressing ballache about this disease =(
This is incredible. I just finished high school and I can understand the key points of this talk. Incredible
Then you went to a good high school.
So much info here!! Each time stamp could be expanded into another stand alone video series.
I have to say, I still cringe every time people use the phrase “caloric restriction” as if all calories (wether fat or carbohydrates) metabolize to energy the same. They’re assuming humans and animals are calorimeters.
Also, far too many researchers incorrectly assume that ketogenesis is not a normal state of human metabolism and that ketones cannot be our primary source of energy.
Let’s at least be sure to correct researchers who claim that a low carb diet is up to 20% of calories from carbohydrate when in fact a low carb diet should be closer to 5% or at least low enough to encourage lipolysis and maintenance of a low level of serum ketones.
I wish that in English we had one word for emotional stress and a separate word for physical stress. It can be muddy using the word in both capacities.
49:00 then why do they always tell people on chemo to eat a lot of food while in therapy? To me it sounds like, from this information shared here, that fasting during chemo therapy can be beneficial.