Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation 

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).

I consider myself very fortunate to be living in an age when this type of information is so readily available to the common man.

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.

I really appreciate your interview technique - you let the guest talk, and then summarize and help expand the guest's points. Thank you!

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.

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

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.

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.

This was an excellent episode. What a brilliant mind, and a superb moderator/scientist asking all the right questions. Fascinating!

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!

The way Dr. Kroemer pronounces autophagy is borderline ASMR. I could listen to 9 more hours of this.

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🇺🇸

This became my favorite youtube channel in less than 24h, the best ever! Big hello from East Europe!

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 guy is the real deal. He's got 'skills to pay the bills'.

This is one of the best interviews I've seen on this channel! Super comprehensive!!!!

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

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.

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

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.

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.

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 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!!!

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!!

Another excellent interview, Dr. Patrick. You maximized this opportunity! Thanks so much to both Docs, and soon I'll be supporting at Patreon.

wow this guy is excellent. thank you so much for interviewing him!!

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.

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. :)

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.

Excellent interview! Thank you. Have you re-interviewed Guido again since then, with more recent advances in his research? Thank you. Greetings fro Australis.

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.

Dr.Patrick is one of the best interviewers. Fantastic information. Keep up the good work!

Thank you both..I could not stop watching. Very enlightening

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!

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

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

I would to shore our discoveries a Cancer Survivor !

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

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!

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.

Appreciate this great video from two wonderful people.

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.

Real smooth way of asking Rhonda out for a drink doc!

Congratulations on your pregnancy!! wish you all the best!!

This is the best page I’ve ever discovered

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.

The on-screen footnotes are a nice touch.

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

How lucky are we man. great interview

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 =)

You're really knockin us out with these videos... It's exciting and I'm grateful that you post them. Thank you

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.

Congratulations on the baby! You look beautiful.

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!

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!❤

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.

His accent automatically gives him more credibility. Great interview!

This is just brilliant.

So it takes a minimum of 3 days of fasting before a meaningful level autophagy is activated. Interesting!

Definitely watching this when I get out of work. Thank you Dr. Rhonda!!!

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

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.

I don't even consider a 14 hour fast mentionable as a fast.

How can this possibly so interesting that I don't want to even pause it?

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.

wow thanks for writing down the biology terms as he was describing this stuff, I really do appreciate that very helpful!

Amazing! I started it over right after it finished playing. Thanks Dr. Patrick

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

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

spermadine found in sperm is a great anti aging treatment! I've got to get my wife to buy into this!

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 man is a wizard.

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!

I would love to hear his vision about the effectiveness of dry-fasting

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.

What an awesome guy. I gotta start drinking coffee now.

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

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

Very interesting talk, thank you.

This is incredible. I just finished high school and I can understand the key points of this talk. Incredible

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!

16:56 does intermittent fasting induce autophagy?

I just finished an 8 day water fast

The 'M' in MToR is 'Mammalian'; it accounts for insulin and such in critters with complex cells, as opposed to yeast and such.

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

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 wonderfully done Thank you Dr. Rhonda you’re amazing!

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!!!!

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.

This is fantastic information thank you so much for making all this knowledge so easily available!

Yes I do love theses podcasts

awesome geeky informative motivating discussion. Thank you.

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.

Maybe I haven't heard it yet- but do you not consume any form of dandelions? The leaves are incredibly nutritious, the roots are great as well. I'd love to hear you talk about them :)

Great interview, thank you both!

Awesome video, very informative!