Insulin Makes your Mitochondria Young and PINK
ฝัง
- เผยแพร่เมื่อ 7 ก.ค. 2024
- Nature Metabolism Paper: www.nature.com/articles/s4225...
Chapters
0:00 - Introduction, Mitophagy
1: 31 - New paper about PINK
2:14 - Core mechanism
5:37 - Looking at the data, Pretty Pink Pictures
6:41 - ApoE4, the Alzheimer’s risk factor
8:42 - Relevance. Fasting and Feeding cycles
10:13 - My intellectual ecosystem - วิทยาศาสตร์และเทคโนโลยี
One of the things that I truly appreciate about your channel is that you take incredibly complicated scientific studies and concepts and translate them in to simple language for the rest of us. I want to know about all of the scientific research going on out there, but there is no way that I could read and understand it myself.
Thank you! That means a lot!
Eat carnivore omad walking fasting ice bading zeolith sun d3 NAC msm borax dmso never ever take the clot shot seed oils sugar and carbs oxalates processed food pestozides
I don't listen to intellectuals unless they can credibly wear a sleeveless shirt.
This. Thanks for that!
No, same here!
Am I the only one who thinks that a fit intellectual in a sleeveless cut off shirt is awesome?
I like you!
@@nicknorwitzPhD The feeling is mutual!
Sounds great, but not always possible. In the beginning, 120 hr work week plus classes. Then supervision of others and 24 hr on call, then private practice with a whole new set of problems. Or the ones that dedicate their life to science, studies ,...Sacrificing everything for their passion. Think of an Albert Einstein or a Tesla. Think of a Walter Willett....many examples. Not an easy path. Stress, job demands....then if a wife or kids involved, never seen a ripped / jacked +200 lbs physician or professor that wasn't divorced. Lots of trade offs. Something has to give.
@@DrAJ_LatinAmerica I agree... and medicine and healthcare are changing... I'm in the process if figuring out my priorities and what will give. But you're right... can't be a researcher, physician, public educator, healthy, and a good partner and parent...
It makes me want to give him a hug
Here's my recall from a single watch-through:
1) Brain has neurons
2) They need lots of energy
3) They are sorta like octopi...octopuses?.. - they have a large main mass which had many "arms".
4) For some reason they need mitochondria at the end of the arms to "turn over" at a specific time and not all the time.
5) Insulin triggers the "turnover" somehow
6) Insulin resistance can f•ck up the ability for the mitochobdria to get the memo from insulin
7) This means the mitochondria don't "turn over" at the right time and get old or something
In other words, insulin resistance can negatively effect brain health.
❤
Long story short….pretty much
further simplifying the simplified 👍
So go on a ketogenic diet.
@@calebrobinson7277 No not ketogenic, time restricted eating, its the cycle that counts, not constant keto
Such a excellent level of detail. Thank you for doing these types of educational videos!!!
Thank you very much!
Impressive unpacking of complex studies in just a few minutes...graphics & reading very supportive. Speed is good...don't slow it down.
I don't have a "slow" button... ask anyone who knows me. And THANKS!
We can adjust the YT speed of the video though 😂
As a physician with a degree in nutrition, I am amazed and joy filled being educated and entertained by your channel. Great balance and remember…..Stay Curious!
I appreciate that! Thank you kindly!
I love your approach and your sense of humour. Keep up the good work and please keep being your authentic self.
Appreciate you :)
My father and I have ApoE3/4 and my grandfather had Alzheimers. I find this EXTREMELY critical information for my father and I!
Sorry about your father. I'm ApoE4/4... but I think gene editing is very promising ... MIT doing some AMAZING stuff...
How does it help? Is there any preventative action he can take with this info? Should he be doing things to increase his insulin?
@@supercal333intermittent fasting helps
@@supercal333the idea is to increase sensitivity
@@supercal333I don't think you necessarily want to increase insulin but you do want to increase insulin sensitivity. This is a highly debated topic. The low carb people will tell you that reducing carbs will increase sensitivity but the plant based people will tell you fat reduces sensitivity and that you need to eat very low fat high carb. Who do we believe. But I think that intermittent fasting is universally agreed to help insulin sensitivity so, if nothing else, just extending your overnight fast is going to help. As for which dietary interventions you take, you need to do lots of research and decide for yourself what you think makes the most sense.
Thank you Nick for continuing to educate all of us as to how the human body metabolism actually works. Bravo! 🙂
You're welcome!
Love your research and willingness to share! Keep up the great work, and Stay Curious!
Stay Curious!!!
I think the speed, animation, etc, are all really good.
Cheers man!
What I appreciate about your science communication is that you’re not looking to take findings from papers and use them to assign “good” and “bad” labels to various things. I think I have a tendency to do that when I’m reading papers on my own, just as a means of simplification.
You get me!
Every time you speak, you say something interesting, whether using celery, Oreos, AMPK, or mitocondria. I love it all! Keep it going.
Thanks! 😃
I think this video was very well done with a breakdown and explanation that I can understand. I thought the graphics were well-matched to the narrative. Also, I appreciated your recognition of your tendency to speak rapidly. You then slowed down which resulted in my being able to more easily follow what you were saying. I enjoy all your videos, tho must admit a few have been way over my head. But please, keep putting out your content. I’m always learning something from you. Thank you!!
Thank you!
I like when you explain the science. You make it understandable. Most of the time when I have to rewind is when I get distracted and not because you’ve lost me with your explanation. I enjoy all of your videos and appreciate the education. I also appreciate the respectful presentation of the information.
Thanks so much for the kind words and feedback
You must be getting the content right. Every time I see a new one I make time to watch it.
I often spend time afterwards looking up more details on the complex things you cover.
I like the graphics & charts you add. These are very helpful for me to understand.
Yes! Both and! Always appreciate your approach and good to hear "another side" to what "experts" in the HC industry have spouted as "known and settled science" for decades.
Definitely not settled science! Science that's settled is boring anyway
First, your excitement for all your topics is infectious! Second, I have yet to see one of your videos that didn't teach me something new, present a different way of looking at something I already knew, and/or engage and entertain. Don't change; just continue to grow you. Thank you for sharing your time, knowledge, and understanding.
Always love the thought provoking content. Keep them coming.
Will do!
Great video again. So fascinating
You're very welcome!
Love this delivery and graphics. I think visibly seeing the connection points and written captions helps me understand better.
Happy you're happy :)
SO grateful and excited to try to understand all this! Thanks so much for the careful and fascinating way you create this opportunity for all of us to at least begin to understand! I did reverse Type 2 and pre-diabetes with low carb keto, and dropped some fat...with 16:8 as well!
Thanks! And go you!
This kind of videos are best! Unpacking different studies etc.
Glad you enjoy them!
Yes I appreciate the dense content. Your explanation and graphics help a lot. Keep it up, you are giving me a metabolic education for way less money than you have spent on your education! Thanks.
Ya, that's true... by A LOT!
I like your variety of approaches to engage your audience. This video is by far the most interesting lead in to intermittent fasting that I have seen. You show the biochemistry of why you should do it. I like your intellectual approach even if I have to watch it five times to understand it. Thanks for sharing.
I appreciate that!
Love this channel, one of the best.
AWEEE!!! So kind!
great channel .wonderful clear precise explanations.dont change
Thanks! I will evolve though... evolve or die
I love that you break it all down, I definitely appreciate the slightly slower pace of this video.
I also really appreciate yours and Dave's approach as curious scientists willing to follow where the science leads and not just trying to make it say what you want it to.
I can't stand the aragance of some of your detractors.
Keep up the good work!
I thought Alzheimer’s Disease was thought to be a disease of insulin resistance of the brain? And that a diet that decreases circulating insulin levels promotes mitochondrial health in general, especially in the brain. So are these benefits of PINK1 decreased in those of us following a low carb lifestyle?
It almost sounds opposite of what we've been talk recently about insulin, so maybe i'm not understanding
There's a relationship between IR and AD, but it's not quite so linear. I think engaging in a lifestyle that improves metabolic health will overall serve one well in preventing AD
I appreciate your gifts of these well-paced, tight explanations. Your curiosity and enthusiasm shine!
I enjoy the balance!! Love the science but also love the practical ideas! you explain complex science in easy to understand terms!! 💕💕
Thank you very much :).
I like the variety. Good work and very thoughtful design.
Yup.. your videos are fascinating ..love the science!
Glad you enjoy it!
I absolutelly adore your channel. Nothing to be chanched. I am 67 and not native english speaker (if it matters)
Wow, thank you! And you feel this was clear enough to understand?
Beautiful video, Nick. Nice job
Thank you very much!
I'm in awe of the science 🤗
Yas 👏
I'm addicted to physiology and the quirks of metabolism and at this point, I'm drowning. I need 2 lifetimes to understand how we work.
Just 2? ;)
Good explanation, Nick, both with the cellular science and to tie it in near the end of the vid, stressing that the ebbs and flows in our bods when we fast tie into how an insulin spike prompts needed mitochondrial autophagy in our neurons. Kudos, and thanks.
You're welcome Carrier Sailor
This is well presented thank you.
Glad it was helpful!
I really enjoyed the presentation style / approach: it was refreshing and engaging. The graphics were really good! Pace of delivery was just fine. I found the subject really interesting, particularly as my own background is in physiology / pathology. Definitely subscribing 😀.
MORE! WE WANT MORE! I actually started making notes
Yay!!!!
My dad died of dementia two years ago. Great content, great presentation. Thank you!
Sorry about your dad. That’s really hard. Glad you enjoyed the video
Studies into APOE4 in 3rd world countries show it drives cognitive fortitude to adverse environments.
Prevents cognitive decline from starvation or toxic exposures.
I really appreciated this video. Though it had a lot of info the speed was a lot easier to follow. Thanks!
you're welcome! thanks for the feedback
I think you're doing great. I enjoy your videos even if I glaze over momentarily at times. Even when that happens you generally clarify it afterwards. Thanks for all your work we appreciate it. On a side note, I've been intermittent fasting for 3 years this month and feel terrific at 60. Initially lost 40 lb in the first few months and have kept it off ever since. I'm not perfect all the time and pivot for social situations Etc. I really believe if you do it 80% of the time you're going to be in great shape!
For me personally, I love the deep dense dives, but the "baity" videos are fun and are more helpful for the ketovore support group I lead. I think you are striking an excellent balance and I really enjoy the content you are bringing to the table. So, Thank you!!
*keto
Appreciating the cool science in process ....
Appreciate you :)
I enjoy many of your videos, some I only watch a bit and some I watch two or three times, like this one so I think your balance of content is good.
This one is especially interesting as my step mom has advanced alzheimer's.
Appreciate it. And I'm very sorry about your step mom. That's rough.
Am i right to say that this applies most to neuron cells? Mitophagy in other cells in the body may behave differently? Since its counter intuitive that keep insulin low is good for health but at the same tiem bad as it suppression mitophagy?
Listening to this makes me realise how limited my brain is!
Trying to make the connection between insulin and fasting. Also wonder how low carb factors in. Is this essentially suggesting insulin resistance is bad for mitophagy? (Therefore fasting can help?)
Your explanation of the process I thought was excellent and I found myself waiting for the timing of the process. I then realized mytophagy goes on constantly depending on the need to replace the mitochondria but will be inhibited by insulin resistance. Also intermittent fasting which leads to lower insulin and systemic autophagy is also beneficial for mytophagy. Hope I got this right.
i appreciate the pure science and research.
Thank you!
I have 2 copies of APOe4. I started keto a few months ago. So does this mean I need a longer fasting window to increase mitophagy.
Thank you, Nick! I am very interested in mitochondria since taking and discontinuing a statin. It was bad for my brain and body. Recovery has been slow.
I think you have great content that is well explained even when very complex
Thanks 😊
KEEP DOING WHAT YOU ARE DOING.
Cheers! Will do
Thank you. This really helped me understand why Dr Dale Bredesen recommends intermittent fasting along with ketosis for an APOE4/4.
I have a question. I am a bit late, so I hope it still gets answered.
If I am on a keto diet and my insuline is most of the time low. Does it mean mitophagy isn't happening? And this also a risk factor for Alzheimers? Should I sometimes raise my insulin with a little bit of carbs? Or is there a different mechanism at work?
From what I gathered a ketogenic diet would not be ideal, which I am not sure I want to believe. 😊
I don’t understand what this means I have to do as a low insulin key compliant keto diabetic?
Cool that you wrap-up with what I see as: 1. A super short summary and 2. A TAKEAWAY FOR ACTION (as here, where you suggest some kind of IF - which you do yourself too)
Best regards / Henrik / Denmark
Thanks Henrik! Appreciate you!
I've heard about ApoE4 for years, but this was the first time I got an explanation of how it could impair brain health.
Complex gene variant… lots to learn about it
Nick , that was awesome. Can you go over the Randal cycle?
Hi from Japan!
Thank you for sharing such interesting studies on your channel!
In this video, the study says that Mitophagy occurs when AMPK is off due to insulin signalling. Would that mean that most mitophagy occurs postprandially?
It challenges the common idea that mitophagy happens during prolonged fasting states. Please elaborate.
Watch the video again -- carefully -- yes there is a counterintuitive aspect that you're keenly picking up on... one of the things in this paper that struck me... good catch!
@@nicknorwitzPhD Thank you for your reply. Are you pointing out at the ebbs and flows section of the video?
In other words, fasting will improve insulin sensitivity which may in turn increase mitophagy postprandially.
It would be interesting to see how strong and how long the insulin signal needs to be in order to initiate mitophagy…one possible question: are slow long meals better than short ones or vice versa?
I like your videos, no matter the style.
Thanks :)
Really interesting that you asked for our input. This video was very complex and I am an MD. I think it was right on the edge of too dense and a bit too rapid on the speech meter, but not bad. I would suggest just a little slower on the speech delivery and graphic presentation. That way we can really "get" your message instead of having the possible reaction of giving up and saying to ourselves "I can't keep up". My experience with patients and colleagues is that when we are deeply into a subject we want to blurt out the information as quickly as possible, but for the listener, when the information is being heard for the first time, this can be overwhelming. It is always so hard to step into the shoes of the first time listener and requires real constant attention to that so that communication, which is the goal of course, is robust. I applaud the work you are doing in the world. You are making a difference and countering the creeping cynicism that is occurring in medical science these days. Thanks you for contributing to us and keeping our enthusiasm alive.
Serious question and no offense intended... I'm curious whom you and also Nick think are the target audiences for this video. As someone without a scientific background I found it clear and the animation able to have what was being said "click" for me as they were being said. I think videos need to be targeted specifically for an audience and only that audience. If multiple videos need to be made, fine, but they should not be slow and bore the heck out of whatever audience I fit into simply to cater to the slower information processors unless those are who Nick is wanting to target (which I doubt).
As someone who doesn’t have an MD, I found this video perfect. I think the speed of speech is perfect. Any slower an I would be speeding up the video 1.5-2x speed. There are a lot of people out there who listen to videos at a faster speed in Yt, so you have to realize there are more than doctors watching this and also understanding that your preference for speed doesn’t necessarily represent the majority.
"t is always so hard to step into the shoes of the first time listener and requires real constant attention" -- really well put... "You are making a difference and countering the creeping cynicism that is occurring in medical science these days. Thanks you for contributing to us and keeping our enthusiasm alive." - Appreciate this and appreciate the feedback. Best wishes!
1) Great video as always Nick! You continue to open my eyes to neuronced (6/10 pun?) areas of science and such a wide variety of fascinating literature!
2)If I am interpreting this correctly the production of insulin (Presumably bolus insulin) inhibits AMPK and turns on necessary mitophagy. However the frequency of these insulin spikes may lead to unbalanced mitochondrial turnover and eventually reduced ability to turnover when necessary.
3) Do you think perhaps it occurs post prandially as there is readily available energy coming in for the body and cells to use to breakdown and build new mitochondria?
4) Do we know if all mitochondria in neurons undergo mitophagy every time in the presence of insulin or are there other signaling molecules or mechanisms that prevent every mitochondria from being turned over if they have recently been created?
Would love to know your thoughts and no stress if you don't have the time to answer! I will keep learning!
@00:29 "This creates a spatial problem..." A lot of my friends say _I'm_ spatial. At least I think that's what they're saying. Does that mean I'm brainy, or nervy?
*@**4:19** NOTE: AMPK can be disabled by polyol, one of the intermediate metabolic steps of the break-down of fructose. Fructose levels in the brain and spinal cord are the CNS's response to osmotic pressure generated by sugar levels in the rest of the body, outside the blood-brain-spinal cord barrier. Motto of the story: cut out all sugars, and all carbs possible.*
This video was great thank you. It was really cool to have a breakdown of a recent paper in biology and understand most of what was going on. I don't think you talk too fast. Apart from when you read out the title of the paper which you obviously did fast intentionally, but that's a bit like "I'm assuming you won't be able to understand this". I think if you had read it out slowly then I would have been able to understand it
Glad it was helpful!
OK so what should us that have the ApoE4 ultimately be doing beyond LC/Keto/Carni/IF & healthy metabolism??? I actually have 2 copies of ApoE4 😟.
Your sincerity is your greatest gift. I still have a hard time following some of your stuff, but I enjoy watching it. This video I'm left with 1. does everyone have apoe4 and 3 cause it sounds like yes. 2. If it is yes how do you know you "turned it on." 3. So is insulin the bad guy in this or the good guy? It sounds like the good guy if we need it for mitophagy? I'll watch it again, but I'm left a little overwhelmed.
Thanks for all the geeky science stuff. I think it’s 😎 cool!
You bet!
I like the density. I don’t mind the baiting as long as it leads to something dense and thought-provoking.
Then welcome to my channel… you will be satisfied!
So, I don't think you said it, but insulin resistance plays into this, right? So perpetually high insulin affects dysfunction in this context?
Wondering if you'd be up for addressing / weaving in an axiom I ran into : "insulin suppresses autophagy."
Sure: “simplicity is the death of nuance” is my answer
One thing you could add is information at the end of each video that is actionable for people trying to optimize their health. Tie the topic to practicle changes in behavior that would be beneficial. It's a stretch I know but could be very useful.
Interesting but that would suggest that IR, consistently high Insulin, would trigger consistent mitochondrial turnover.. which would tend to reduce things like Altzhimers, but the data shows that IR increases risk. Makes me wonder if there is a habituation or other effect that eventually reduces the effectiveness of the pink turnover for chronic high insulin....
Do a mix. We also want to see “normal Nick”… everyday Nick like if you go to your mothers house do you eat the food she gives you or are you a total OCD foodie? I do like your science ones but as we all know scientists are sometimes looking into the black hole but never pull their heads out to see the bigger picture and sometimes miss the truth
Ironically I just closed a recording video talking about my (our) summer projects of making cheesecakes with my girlfriend, who is not keto. At my mother's house, I do the cooking ;). And, yes, I'm very happy to make normal desserts and sweet potato side dishes for those who enjoy them. I "do me" so to speak as I use a KD therapeutically.
Hi doctor thanks a lot for the videos, I really appreciate the content. I would like to ask you a question. Do slightly over-physiological doses of testosterone interfere with the process of autophagy and mitophagy? I ask because insulin is an anabolic hormone and so is testosterone. I ask my doctor but he doesn't know. Thanks again.
Does it mean that we that live on a low-carb or ketogenic diet and little insulin release are exposed to less mitophagy?
Not necessarily, no. Typically very insulin sensitive and people on KD still release insulin with food intake
I was searching NN’s store for a Dayspring t-shirt.
The pictures of the merge might as well be pictures of a distant galaxy. Beautiful
They are!
So what's the action to be taken here. Should we be trying to increase our insulin to prevent neurodegenerative diseases as we age?
So low sugar and carb diets are bad now? Cheat meal once a week or month are good?
I didn’t say that… not in the slightest
So stay low sugar and carb. Increase insulin sensitivity by all means necessary?
This was super hard to follow while having my eggs bene 😂 which probably didnt help, im usually always multitasking (working out, chores, driving etc) when watching or listening to YT.
The animation is always improving so youre nailing that part, and it helped to keep me locked in (compared to Laynes latest vid on protein which just showed a diagram 😂).
I'm wondering whether you might consider simple analogies if possible to help simplify the logic. There was so much jargon, id probably have to rewatch it 3x with a notepad, and a laptop to lookup definitions etc, which realistically probably wont happen.
I appreciate you doing the work to explain complex science, hopefully my attention span and intellect can keep up.
Good work Nick 👊😎
I’m now confused. I thought that autophagy, which I assume includes mitophagy, is turned on after prolonged fasting, which turns insulin off, and now you are saying that insulin through inhibiting ampk turns mitophagy ON. Where have I gone wrong?
Nope... you caught the counterintuitive aspect of this paper... which they in fact point out and which captured me. The body is complex and different spaces, organs, cells and sub compartment in cells can operate in different ways. COOL RIGHT?!
@@nicknorwitzPhD Yes, that is cool, explaining why, as you said, cerebral insulin resistance can have such a devastating effect
1) I don’t see the relationship between the first part of the video with cycling on and off eating. 10:45
2) We are told we need to lower our insulin to get into autophagy. This Petri dish study says insulin triggers mitochondria autophagy. ??
Thanks Nick! Do you have any thoughts on why someones liver would decide to make "high " amounts of sugar every morning after doing super low carb for 8 years?
Asking for a friend.
Bob the welder.
Depends on what "high" means and how much protein he's eating. If he's eating a lot of protein in one sitting, then gluconeogenesis is probably why. That's my best guess.
Low carb diet is know to cause physiological insulin resistance. This is not enough to lead to diabetes but will produce an elevated fasting glucose. There’s no reason to believe this is a problem because it not pathological (not associated with disease).
I believe, on a low carb or ketogenic diat, the liver need to make more glucose to deliver the demand in my experience, especially if you make much endurance exercise.
@KarlKrassnitzer-mm8wb thank you!
When we fast, insulin levels are low, it spikes when we eat, especially carbs. So, does that mean there is no mitophagy when we fast and it only activates when we eat? The current view is that fasting promotes mitophagy. Could you clarify? Thank you. Love your channel, btw.
No b/c cell and spatially specific. Autophagy can happen at different times in different places in the body + & you're always producing insulin, so a function of insulin and sensitivity + you release some insulin in response to food even if there aren't carbs (assuming not T1D)
If you get bored study CFIDS, MCS and connective tissue problems like fibromyalgia.
Personally, I enjoy both of your approaches
Awesome, thank you!
RE: ebb and flow, it makes sense that insulin is elevated when cell energy is elevated; that is the condition under which mitophagy takes place.
IMO You have a good blend of content. Prob something like a 3:1 ratio of dense to the celery type.
Can you address Neuropathy? Sounds like you are addressing the diabetic side effect of nerve damage due to diet.
All this is fascinating. If you could zoom out and speculate at the disease level, could this be why diabetics have a higher rate of Alzheimer's? I've often heard that APOE4 is the wild type, the one most of our hunter-gatherer ancestors would have had? So, fasting which would mimic their feast and famine cycles in nature, would be advantageous. Then my question is there must be some instances when not having efficient mitophagy is an advantage in nature?
Oh, does it mean keto could hamper mitophagy bacause it keeps insulin low?
That's my question too...some have surmised and it's kind of been my experience that occasional "cycling" seems to be beneficial...staying flexible AND maybe this is allot of why I feel better after cycling off Keto occasionally, or maybe I'm still just a sugar junkie getting my occasional fix. I will say that when I needed to lose weight cycling seemed to break the "stalls", YMMV..
What are the times you fast? Are you skipping breakfast if so are you aware of the studies that say this might increase LDL?
I usually practice 16-8 with my first meal around 1030 am and dinner around 6 pm if I have my choice.
So if Insulin is good for your brain, does that mean we should eat more carbs to get more insulin?
I think you should offer yourself as a speaker on the Low Carb Cruise. Next one goes to Alaska next year. I am about to go on this years cruise tomorrow. Feldman will be there. You should be on the 2025.
makes sense, it's cool when when there is no pollitics injected or industry related zig-zags of information and you say things straight :D
I try my best :)
Spending a little more time explaining the relationships between the enzymes in the core mechanism would help lay people understand what is doing what, where. Knowing your audience is important as you traverse this journey. I appreciate the video, and will share it on social media. Subscribed for more Biochemistry research discussion.