Autophagy: the Truths, the Myths and the Science
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- Опубліковано 12 тра 2024
- Which behaviors induce & suppress Autophagy? Can we have too much autophagy? Does autophagy affect cancer and aging? Two research scientists discuss common ideas on autophagy and the science behind them.
Nicolas´ channel (Physionic): / @physionic
Connect with Gil:
Facebook: / drgilcarvalho
Twitter: / nutritionmades3
Animations: Even Topland @toplandmedia
References:
1-skeletalmusclejournal.biomedc...
2-www.ncbi.nlm.nih.gov/pmc/arti...
3-www.molbiolcell.org/doi/full/...
4-academic.oup.com/nutritionrev...
5-onlinelibrary.wiley.com/doi/a...
6-www.nature.com/articles/cr201...
7-www.ncbi.nlm.nih.gov/pmc/arti...
8-www.ncbi.nlm.nih.gov/pmc/arti... IF & CR cause autophagy
www.sciencedirect.com/science...
9-www.ncbi.nlm.nih.gov/pmc/arti...
10-www.mdpi.com/2073-4409/8/2/123
11-www.sciencedirect.com/science... ox stress
12-www.mdpi.com/2072-6694/13/3/533
www.ncbi.nlm.nih.gov/pmc/arti...
13-pubmed.ncbi.nlm.nih.gov/17018... autophagy & cancer effect varies
14-www.mdpi.com/2072-6694/13/14/...
15-aacrjournals.org/cancerdiscov... chemotherapy
16-www.ncbi.nlm.nih.gov/pmc/arti...
17-www.sciencedirect.com/science... 17-19h fasting
18-www.mdpi.com/2072-6643/11/6/1234 18h
19-www.ncbi.nlm.nih.gov/pmc/arti... 72h water fasting
20-www.tandfonline.com/doi/abs/1... nematode lifespan
21-www.nature.com/articles/s4358... autophagy decreases w age
22-www.sciencedirect.com/science... lysosome w age
23-journals.sagepub.com/doi/abs/... exercise & glutathione
24-www.ncbi.nlm.nih.gov/pmc/arti... 72h fasting loss little muscle
25-pubmed.ncbi.nlm.nih.gov/37377...
Disclaimer: The contents of this video are for informational purposes only and are not intended to be medical advice, diagnosis, or treatment, nor to replace medical care. The information presented herein is accurate and conforms to the available scientific evidence to the best of the author's knowledge as of the time of posting. Always seek the advice of your physician or other qualified health provider with any questions regarding any medical condition. Never disregard professional medical advice or delay seeking it because of information contained in Nutrition Made Simple!.
#NutritionMadeSimple #GilCarvalho
0:00 Sneak preview
0:40 Intro
1:44 What is autophagy
4:53 Turning Autophagy ON & OFF
6:49 Exercise and autophagy
8:16 Fasting vs calorie restriction
9:08 Triggers of autophagy
10:53 Autophagy and cancer
13:26 Autophagy nuances
16:13 Timing of Autophagy induction
21:19 Humans vs lab animals
24:44 Measuring Autophagy
27:03 Autophagy & Aging
30:48 Autophagy & muscle loss
32:20 Summary & takeaways
Thanks for having me on, Gil - I had a blast discussing with you; I even managed to hold my bad jokes in check (mostly) 😄.
Thank you both. I learned so much!
Thrilled to hear it! @@Jupiter_Crash
Your jokes are usually pretty good. 😉
When I realized it was you I tapped right away. Such a interesting combo I wasn't expecting.
Thank you both, I’ve been waiting for more clarifications regarding autophagy.
If I may ask.
I think you only gave an example on certain cancers and treatments where increasing autophagy would be negative. However, you mentioned there were many instances where it would have a negative effect. I would be happy if some more examples could be provided.
I’m a type 1 diabetic who had a enormous insulin resistance. I started against my doctors recommendation with ketogenic diet and then intermittent fasting and had enormous results the in first year, now 4 years later I’m not having the same results. Anything I or other should be concerned about regarding inducing autophagy through fasting.
Thank you again to both of you.
Listening to two scientists objectively discuss relevant research in a way that isn't dumbed down and/or agenda-driven is such a rare treat these days. This channel is such an important resource, and I am so appreciative of all you do Gil!
Physionic and Gill on the same video!!!!. 100% upvote before watching.
This channel just keeps proving why it's the one of the best places for nutrition info not just on YT but the entire internet. Always lists refrences, always tries to be unbiased as possible, and brings actual researchers to discuss topics in depth, instead of just using clickbait and "dumbed-down" slogans.
Excellent discussion of a very complex issue. Very important, not very well understood…
How did you of all people end up on this channel?
Mr Berry, an influencer who doesn't sell any products but recommends electrolytes often (due to diet)
Very interesting to see you comment here! Maybe you can have gil on for more exposure? Gil is great.
Love 2 of my favorite fact based youtubers discussing science! Appreciate what you both do, a lot!
Likewise. I have learned so much from these guys!
Gil, this is a very important video and I love seeing you and Nic working together. (He's one of the smartest on UA-cam.)
You always offer no-nonsense, intelligent fare. Many thanks. 🙏
Nicholas is my man crush, his intellect and his humor are so damn attractive, wait even those nerdy glasses allure me!
Jokes apart, if someone is reading this comment, do watch his stuff on YT. That guy is phenomenal.
Best wishes all the way from India 🇮🇳
I love to watch his videos but don't understand anything 😅 still love hearing it out like a podcast of sorts in the background
You know it's going to be a great week when you start it with a video from Dr. Carvalho. Thanks for the great information!
Can't wait to watch! Such an overused buzzzzzword used by many zealots that don't understand it and pushed many influencers that use it to make money off the zealots!
But hey, the truth doesn't sell well does it 😊
I want to thank you for all of the references and the great illustrations and timestamps. Beautiful presentation of a great discussion.
Wow! My two favorite educators TOGETHER! What a treat! Thanks, guys 👍👍
This fellow is good. Please have him back!!
❤❤❤❤❤
One question you touched on was the relationship between fasting and muscle wasting. A more detailed answer at some point would be very helpful. Thanks!
Very enlightening discussion. Shows how nuanced and complex things can be in health and science in general. Thanks to both of you!
Two experts giving great info about this extraordinary topic.
Thank you!
Thank you for presenting real scientist to explain science and misconceptions. We need way more of this and especially explaining how good Research happens and that sometimes it just points to needing more research.
Thanks for having Nicolas on. I love listening to his detailed information.
Very interesting but also sobering discussion. Keeping us centered on what’s known so far.
Excellent conversation. Nick and Dr. Carvalho are some of my favorite health experts.
Was pleasantly surprised to see a thumbnail with 2 of my favorite UA-camrs 😊 great collaboration
Hey Dr. Gill,
Kudos on the fantastic content! I stumbled upon your UA-cam channel during my quest to tackle pre-diabetes through healthier eating. Over the past two months, I've immersed myself in over 30 to 50 hours of podcasts from various experts, and your scientific approach on topics like diet, nutrition, and fasting truly stands out. I am a fan.
With intermittent fasting and a low-carb diet, I managed to shed around 15 kgs. However, I am still trying to find more information and settle down with a sustainable diet that I can carry for the rest of my life. While devouring your videos, I couldn't help but wish for an audio podcast version on platforms like Spotify. It would be incredibly convenient for folks like me who love listening while working.
Keep up the excellent work!
Cheers
Loved this Gil! Would love to see more videos regarding research on ageing.
Hi Gil, I used to love science when I was in school. I’m about your mothers age and I’m learning so much from your channel even if I have to watch it twice to get it all in. Aloha.
Excellent. A big thank you to you and your host for this.
I like both you guys that call out the BS and filter out the noise and make us plebs understand very difficult to grasp subjects. Thank you.
Am subscribed to Phisiconic since he started. In a web of misinformed and influence, his presentations, are the ones you should actually savor. No rumours there. Actual evidence and proof.
The first awesome discussion I see on your channel. Great job!
I love it when scientists admit that they don't know! It's exciting to identify areas for future study and expells simplistic thinking.
As usual, good stuff, I’ll have to start following the Physionic channel also. Thanks.
Yes, I've been following the Physionic channel for a while, it's very informative.
It is unfortunate to see other UA-camrs preach autophagy with such levels of certainty. Sadly, those who preach projecting ultimate authority on a subject are looked at as trusted sources while those who admit that certainty is not yet apparent are viewed with skepticism. People only want easy answers.
What do you mean? Do you mean that autophagy is not essential and it's too bad that UA-camrs are saying that it is? Because Nicolas Verhoeven just said that it was necessary for the natural protein cleanup system in the body and when you distill the logic it's pretty self-evident.
Of course Nicolas has more of a micro view of things. It's his job to be cautious with evidence. But from the 10,000 foot view starting and stopping metabolic processes in the body is not that difficult- by stopping food and continuing high metabolism through body demands via exercise.
My feed has been interesting lately. Drs who claim autophagy, done properly, will consume loose skin from weight loss completely and no surgery will be needed. That autophagy from multi day fasts will completely prevent cancer by consuming all damaged cells in your body. That the proponent looks so young due to the elixir of autophagy.
The faith healers exist in many religions. And it's perfect: if your own autophagy experiences don't bring these results, it's obvious you just werent doing it in the correct manner. 🙄
Fantastic job great discussion
Thank you for this conversation! This was very illuminating, and a great insight into what we know, and what we currently still don't know.
The pictures/animations were also helpful for those of us who need to visualize what is actually occurring to cells - very informative discussion. Cheers!
Nick has some great content. Thanks for this
Intresting topic, great collaboration!
Refreshing to see a scientifically responsible discussion on this topic. Digging the jazz😎
I'm hooked to your videos, there are the most objectives I've seen on You Tube regarding nutrition.
My two favourite health scientists together!! 😊
been waiting for this collab
Samee!
loved this deep dive!
Wow my 2 favorite health research youtubers!
I have been following you both for years, not exactly my favorite topic, i like other topics more but still awesome
2 of my fav channels in one video👍👍
great contents !
Gill I'm hoping you start a podcast where you upload the audio version of these, would make it a lot easier for some of us to tune in. Thanks!
Thank you so much
Thank you for helping me learn science! I've been pounding through mitochondria, melatonin, glucose, autophagy, stem cells, metastasis, mutagenesis, metabolism, why my lymphoma chemotherapy doesn't kill other cancers, fenben, ivermectin, aspirin, biopsies, radiation, germ theory, parasites, viruses, Krebs cycle, electron transport chain, ATP, hematology, lymphatic system, endocrine system, digestive system, and as many other things as can be handled by my beautiful mind. I appreciate all the supporting links you have provided : D Bless you for your service 🙏
Whoa this crossover is 🔥🔥🤘🤘
Good solid video, thanks ❤
Learnt something valuable thanks
Wow! I can't wait to get old so I can try this out!
Yayy! Ive been waiting for this to happen since i saw the Dr Brad Stanfield collaboration
Was hoping these two would meet up for a discussion
Great video, There is more evidence than the video discussion suggested. I agree definitive statements should always be taken with a large grain of salt. Have you seen the studies (mostly case studies) coming out of the True North Health Clinic where they were able to fully reverse Lymphoma in both stage 3 and stage 4 with multiple 21 day water fasts and a 5 year follow up. Of course there is more at play here , like the lowering of MTOR, Insulin and IGF1 levels, but very conclusive human data on this specific form of cancer.
The fasting mimicking data from Valter Longo is also becoming more and more convincing and then you have former soviet data on psychological states in humans (referenced in the Arte documentary called the Science of Fasting)
I would love to know more of the mechanisms causing different types of Autophagy. Look forward to a more in depth series on this. :)
Great info 👍
Love your channel.
Thank you
Great video. I hope my Intermittent Fasting and occasional OMAD will help improve autophagy. That and brisk walks and now pull ups too!
My intuition tells me that not all autophagy is built the same. The exact cells that are being targeted probably vary between different types of exercise, fasting, smoking etc. Would definitely need tons more research to go into that detail.
In this interview oxidative stress is seen as one of the drivers of reduced autophagy when aging. With respect to the gene deterioration part: David Sinclair (longevity expert) claims that this is more due to the epigenome being distorted by mistakes of proteins acting on it and that oxidative stress does not really play a big role.
One of the hopes of his research is to be able to restore the epigenome to it’s youthful state. Perhaps this might then also resurrect autophagy capabilities.
It's good to see John Cusak found work in science.
Reversed aging too it appears. Doing autophagy research must be beneficial.
I would hope this works as well as we think in humans. Its a bit depressing not having much to rely on naturally to heal.
Good show gents.
I would love if you can have a similar discussion with David Sinclair. Thanks you for all your work!
That was fun got em almost all ,..nice 👍😅
Fantastic intro into autophagy. After hearing the very nuanced story of what is currently known and not known today about autophagy, I'm realizing actionable intelligence based on specific scientific data is not possible - yet (as Nicolas alluded to).
So, I find myself falling back onto the evolutionary model of what's most likely to be at least somewhat helpful with little/no evidence it is harmful. That being our ancestors very often had to go days (and sometimes longer) without eating. Or they ate very little within that same timeframe. Their food supplies were not reliable as clockwork as they are today. Food was available sporadically and at unpredictable intervals. To me this strongly suggests we have biological mechanisms fine-tuned via millennia of natural selection for intermittent fasting (i.e. starvation).
I may not understand those mechanisms and there are few scientific papers on them yet, but they *must* exist because that environmental reality forced them into existence over countless generations going back to our prehuman ancestors (and even further back into our ancestral species lineage). So acting on that hunch, I think it wise to recreate or really to conform to that evolutionary process that sculpted our genes and physiology. I think we are likely to discover in the future an organism "fitted" into its environment (and behavior) its ancestors evolved from promotes optimum longevity for obvious reasons.
An interesting flipside to the benefits of intermittent fasting (wrt to its evolutionary origins) would be intermittent gorging. Our ancestors, and pretty much all other living organisms, gorge when a windfall of food is unexpectedly made available. Obviously gorging is a problem the west has today in spades, but it must play a role in the modulation of fasting related autophagy. Adding it to the research mix and oscillating back and forth may be a fruitful topic to explore in the future.
If it is true that ancient humans regularly had food shortages it suggests to me only that humans perhaps have adaptations that allow them to survive sufficiently to procreate. Repeated lack of food could still be harmful to both adults and children. In fact we're likely to have many adaptations that allowed humans to not die long enough to make children and enough children so that some of them survived long enough to repeat the cycle. Any or all of those adaptations could have long-term negative consequences. Then there is the fact that evidence suggests that ancient humans typically did not regularly have to go without food.
Somewhere in this video, a question that came to mind is, if you exercise after a period of fasting (whatever that period may be), might that combination of fasting and exercise increase the rate of autophagy? I'm not expecting an answer necessarily. I'm just wondering out loud.
thank you for clarifying that the science is not quite conclusive for the benefits of autophagy for humans, and especially for fasting and exercise. We need to wait for further advances in science to increase our understanding.
What about "glucose:ketone index" for a barometer of autophagy?
Thank you for the clarification regarding autophagy. I read the books on longevity that were popular several years ago that did use non-human studies. I tried expensive fast mimicking diets to "activate" autophagy. I appreciate being informed regarding the limitations of that research. Exercise is free!
Regarding autophagy in mice and men, what one should consider is that a one-day fast in a mouse corresponds to at least a fourteen-day fast in a man. If people see very interesting results in mice and try to replicate those in men using the same timespan, instead of the "equivalent" timespan, they are bound to fail. By the same token, when Valter Longo has extraordinary results in mice coupling fast (one day) and chemotherapy, then he cannot have (and hasn't) the same extraordinary result in men, coupling one-day fast and chemotherapy. The best results he gets and describes in his book are always with people doing long-term fasts (one week or more) and then beginning chemotherapy while maintaining the fast.
On the other hand, clinical studies in humans are at the moment impossible to make properly in this matter because, in the present cultural situation, people are so scared to fast for more than one day that Valter Longo describes how even people in serious clinical conditions refuse to fast because they are afraid to die (!).
Great video. The only thing missing in the middle was an ad for an autophagy-inducing supplement! (joke)
I like this guy if only for his humility and sense of humor in his videos.
collab of the year, like in advance👍
Thanks a lot. Asking for resources for claims on reddit sometimes literally gets you downvotes and hate comments, it's so funny.
Should you continue to exercise while fasting and if so, at what level?
what about sacropenia as we age? I am 80 years old. Is it true that I cannot use fast-twitch muscle fibers as much as
Interesting.
Ok. Nex time ypu talk about exercises you should state what type such as high or low intensity, etc so we can have a clearer picture.
Does restricting calories a bit help (assuming I'm eating in the range that won't cause me, at a healthy weight, to lose or gain weight)? Cuz I read that the body can adjust energy expenditure to what it is provided, so I was wondering if eating at the lower range of the energy expenditure that the body can take is more beneficial than eating at the higher range where we can still be in a caloric balance.
more than amazing! instalike
You and Nick are the only ones worth watching
How do they gauge autophagy? Is it analysis of biochemistry after a fast?
With a keto mojo monitor...
Here come people sharing their personal Anecdote about Autophagy.
I can tell you didn’t listen at all.
@@Jupiter_Crash nah just want to predict the future .
@@Jupiter_Crash You must be new. Every time a video like this comes out, people share their unqualified anecdotes as if they have any relevance to anybody but themselves or if it's even related to the context of what's being discussed.
@@Jupiter_CrashThe comment was not about this video but other comments.
I did water-only fasting for 2 weeks in April 2018. 18 months later, I was diagnosed with thyroid cancer. Do you think its possible the extended fast caused the cancer? I never had thyroid problems any time in life up until the tumour was found.
What was your diet adter the fast?
@@drivingbro very slowly introduced food over a period of about 10 days, then back to normal diet
I'm curious about hormonally-driven breast cancer and whether or not to do TRE. I hope to see a video re: effects of autophagy on different types of cancer. We must always be concerned about angiogenesis.
Unless you were drinking irradiated water for those2 weeks(and I'm being sarcastic about that), I think it's virtually impossible ( because I can't cite any studies) that you gave yourself thyroid cancer by not eating.
I hope it was caught early and you make a full recovery. 🙏
I read a couple of books, by Salvatore Simeone and by Roia Melelli, two therapists specializing in therapeutic fasting, and they describe the entire sequence: first (first day or so) it's mostly glycogen consumption and a little bit of autophagy, then you have one day or so of autophagy - you see that also by the fact that your glycogen is over, but your blood glucose goes up - then autophagy tapers down and goes to a minimum and ketosis begins, and at the fourth day or so one is in full ketosis, and the autophagy lasts during the entire fast but it's at its highest during the second day. I gave it for granted that this is common knowledge, not something to mumble about. They actually say that a long fast is better for certain purposes (such as losing weight) rather than many shorter fasts because when one fasts, one goes through the entire process any time: prevalence of glycogen burning, prevalence of autophagy (proteolysis), and prevalence of fat burning, so you have the first two-three days when you are not really in ketosis each time you start a new fast. The body always first replenishes the glycogen reserves after a fast, so one never starts a fast without burning the glycogen reserves first, although there always is a small amount of the all three mechanisms (glycogen tapping, proteolysis and lipolysis) in the body during the fast.
I'm doing OMAD. Would that be considered short fasting regarding your comment?
@@patedwards8844 OMAD is not even fasting "in my book". It is certainly beneficial, because during those hours in which we don't eat there is a small amount of autophagy and "cleansing", but for what I understand what happens is that everyday you (try to) reconstitute your glycogen reserves and the body is mainly nourished through glucose. Little ketosis, and little autophagy, but that little is every day, 365 times a year, so in the long run it helps a lot. If I did OMAD I would buy a glucose meter and a blood ketone meter to see what happens in my body, i.e. if I am in ketosis during part of the day or not. It is entirely possible, especially if the OMAD is of ketogenic style, that you enter ketosis and remain in ketosis all along, which also means that there is a state of autophagy, which is always present in the human body, but is enhanced in the state of ketosis (and even more in the state of ketosis due to real fasting).
OMAD makes you lose weight if you are in a caloric deficit, which is not necessarily the case, because one could eat once a day, and eat for the entire caloric need. Yet, I think it is easy to lose some weight while doing OMAD, i.e. I think it is easy to maintain a constant small caloric deficit. OMAD should, in theory, easily lead to ketosis IF the one meal is ketogenic, and being in ketosis favours the loss of weight.
I have heard we cant store amino acids. Since autophagy break proteins back down into their base amino acids, in times of inadequate essential amino acid intake, does the body use autophagy to recycle old, misfolded proteins to meet the essential amino acid daily needs? If this is the case it supports the idea that diets with lower levels of protein are associated with longevity like in the blue zones. It seems autophagy is driven less by calorific restriction but more by amino acid restriction / demand? Or have i got something wrong here?
excellent question. autophagy does indeed provide amino acids for protein turnover. in fact there are estimates of the amount of proteins being built anew every day in our bodies and its substantially higher than the amount ingested. therefore the difference must come from recycling such as autophagy
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From the Ancient Semitic:
"Yad He Vav He" is what Moshe (Moses) wrote, when Moses asked YaH His Name (Exodus 3)
Ancient Semitic Direct Translation
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He - "Behold the Breath"
Vav - "Behold The NAIL"
Fasting when still young, fit and healthy. I'm a dad of three kids and teach them the basics of health from within, within mind and body.
No need for fast-food, gaming or hyped social activities as Halloween and so. Acknowledge, learn about the social external hypes, but be in awe with our mighty wonderful self, free from nature.
This video can improve a lot by better preparation and structuring.
How about autophagy causing cancer.. can you please explain this?
If I were to guess i would say autophagy would increased due to fasting more than spreading out meals at same calorie count. I would assume if the cell had a break from processing energy it would have more energy available for autophagy regardless if it is overall processing the same caloric intake and nutrients count. I would also assume the rate would also vary depending if the cells really needed to do more cleanup
So some cancer types will catabolize themselves to survive during autophagy, but using that logic wouldn't continuing the autophagy going would eventually force the cancer to starve itself out?
Ive read amazing data on water fasting improving chemo greatly.
Unfortunately nutrition and health is a complicated matter. Not everything can be simple. The body has so many different processes going on. Invitro vs invivo testing for example can give completely different results.
Genetics plays a role too, so what works in one person may not work in another.
@@loganmedia1142 exactly. One thing is fact, what may work for one person may not work for another, as you said. We're all a little different.
Any relation to Paul Verhoeven? 😀
at about 20:00 - it's really not surprising that 17-19 hours has little evidence of a rise, that hardly qualifies as fasting except in the modern world of plenty. And a mouse with it's much higher metabolism, you see autophagy increase in a 24 hour non-feeding period, but that's similar to a human going without food for a week. The 1:1 (day on, day off) intermittent fasting mouse studies that have been frequently done are like taking humans and only allowing them to eat every other week. I've been waiting for that study. ;-) Meanwhile, if you believe Victor Longo's work, it's 4-5 days of water fasting to significantly raise the autophagy rate. And obviously it doesn't keep going up as a normal healthy adult with average body composition can do a 21 day water fast without issues (having a proper refeeding protocol at the end). .
Of course it qualifies as a fast. I'd be curious to know where this idea that it has to be long to be called a fast comes from.
I tend to get the principals of autophagy mixed up with apoptosis.
That is very interesting! Thank you.
I often feel my very best after recovering from an illness… I wonder if Autophagy is a factor?