Sirtuins reduce Insulin Resistance and Mitochondrial Dysfunction

[@Physionic]

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[@ahmedboutaib1007]

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[@fiona1963]

I am merely a retired diabetes nurse and clearly understood your explanation. Thank you it was interesting and filled in a few gaps for me. There is a place for this depth of understanding. Well done.

[@barasra8847]

We used to like highly summarized versions to the point, but after listening to you, it is amazing to know this microscopic level. Thanks

[@Liz_Alfano]

Don’t hold back on the nerding out. I’m here for it.

[@Physionic]

Noted, Elizabeth. Thanks.

[@Physionic]

People wanted my workout routine, so I’ll discuss that in next week’s podcast. Until then, how about some molecular biology?

[@KamranConsultant4Hire]

I'm not sure if your workouts are different now but...please include the workout routine you had when you were experimenting to see if minimal weight training helps to maintain/grow muscles (I'm referrimg to the "only dumbells at home" workout that you have mentioned in another podcast). I'm seeing gains with short, minimal but intense workouts ( thank God) so i'm very interested to learn about your routine.

[@donwinston]

You've got guns. I saw a vein a few times.

[@535Salomon]

Man, I never skip brain day so more molecular biology please ❤😎

[@BLaReina]

*Nic:* "Sometimes I feel like I just, I need to nerd out for a little bit... Hopefully you'll allow me..." *Physionic Subscribers:* 😄👍💯

[@Physionic]

I'll keep it in mind, thanks - makes me happy to know.

[@MeHere650]

No complaints here. I can follow this enough. Need to exercise to increase my sirtuins. That’s the bottom line here.

[@rahulhumanist]

I am a diabetes patient from India, doing my part of research on the subject matter. Many thanks for this presentation.

[@Physionic]

Happy I could help, Rahul.

[@Oscar4u69]

i love this long format videos, it's astounding how complex the cells and their processes are. just the basics are mind blowing 🤯

[@edmaher1]

This form of content is incredibly useful. I have T2D, and through some of this type of content ( other channels ), I was able to learn enough about metabolic pathways, and with some experimentation, identified a carnitine deficiency that was hindering fat metabolism, helping me improve my condition. I am seeking to learn more, and use the information to reason better about my condition

[@2bbossfree]

Me too but it’s very recently developed cancer so I really want to understand metabolic health.

[@TempehBintang]

My god these are the revelations I’ve been looking for! Thank you so much 🎉

[@MSTP03]

“Sirtuins good, mitochondria powerhouse of cell” 😂 These long-form podcasts are excellent, thanks again!

[@Physionic]

Haha, great summary, Mark - thank you.

[@healthscoutptwernergrosse1579]

Don't worry about the depth of detail - that's exactly why I love your explanations 🤗

[@AB-if8pd]

Great series of Mitochondria related subjects and issues happening inside them leading to know where our illnesses starts from. Thanks. Many success in your life.

[@naijaman6639]

Your channel is growing, Nick. I am pleased for you, given the quality stuff you churn out frequently.

[@Physionic]

Thank you. That's really kind of you to say. It's been a long road - I hope the good fortunes continue. I appreciate people like you that have been following along for some time, genuinely.

[@OurWorldOfWonders]

Thw comment about the... "Just tell us in three minutes" How can anyone put years of study into a 3 minute summery. Just tell people that it is okay to not understand every that you are saying... but to some of us who really want to understand our immediate health situation and how to make it better, I appreciate all of the years of work that you have done to get to the point of being able to ex[lain it at this 40 minute simpled down level. When you know how complicated it is... you have a better idea of how to modify your daily routines so that you can live your best life... and it isn't easy or has short cuts but it can change you life if you are willing to put in the effort !!! I Can't thank you enough your videos have been very helpful to me

[@jonthomas9708]

I find your teachings very considerate of your audience who no doubt have very different levels of knowledge. It's mostly too much for me; I don't have the basic knowledge and framework into which to slot new information. Nevertheless I find your stuff more satisfying than many "explanations" of insulin resistance that come off more like uninvestigated hypothesis stated as fact and couched in terms of cells with personalities. It seems to me you have the genuine deep knowledge; you don't vomit it all up at once and if I don't fully grasp what you do explain then that's my fault not yours. You're pitching at a level that provides a rare value. Thanks for the education!

[@Physionic]

You don't know how much this means to me, Jon. I try my best not to water things down, but I do try to keep in mind not everyone has a science background. Thank you for speaking up - you're really kind.

[@user-mm8jv3tn2l]

Loved your explanations. It gave me alot of inside into the mitochondria and the processes that take place. It is fascinating to get a glimpse of the many different ways that the Sirt. Work to effect so many aspects of the mitochondria and dna repair along with the regulatory functions. Very well explained. I enjoyed the "needing out" Thanks, RSB

[@DanielVictori]

Excellent video. Keep on with great content!

[@Physionic]

Thanks, will do!

[@mathfaster]

While watching I googled "how to increase sirtuins' and "sirtuins and insulin resistance". Lol. Very interesting video. Heard about sirtuins before but never knew what they did. Thanks.

[@jamesoliver6625]

Don't apologize for tracing the chemistry involved. That's exactly why I follow Mobeed Sayed's channel. With two biochemical researchers for parents that was normal dinnertime conversations a kid in the 60. The both worked for the Clayton Foundation in protein structure research, my dad through electron diffraction analysis of protein crystals, my mom as lab tech for a postdoctoral fellow in the next lab to my dad's. I learned a lot of organic chemistry by osmosis.

[@Naomi_kyo]

Thank you for making the slides, the pictures help me learn and remember the key terms :)

[@Physionic]

My pleasure, Cindy.

[@palumpura898]

i appreciate your approach, and your desire to be somewhat thorough

[@lawrencerosier5734]

You are doing it right. I am following you with just knowing about sirtuins etc. from David Sinclair pod casts. I graduated from University of Missouri in engineering ln 1961.

[@colinkelley6493]

I did not understand everything, but what I did understand really helps me. Thank you.

[@richiprosadmistry414]

❤ the details. Need more of these.

[@medicalpanorama]

Chemistry is mechanics. For most people, they just want to know “does it run or not?” But for a few, we have to know the “mechanics” to develop new remedies. The sirtuins and telomerase seems gaining all attention for anti-aging effect.

[@1eingram]

Just bought a textbook on cell biology. Fascinating.

[@jasonhowarth6789]

Isn't it? I still have my huge textbook from my freshman seminar Cellular Biology 255 (smaller class for students with a strong background in biology) I remember titration giving me a hard time. So cool learning about the way proteins are folded on the primary, secondary, tertiary, and quaternary stages. The whole process in which a cell goes through mitosis interphase, prophase, metaphase, anaphase, and telophase. Brings back so many memories from 91'. As well as Nirvana and Smells Like Teen Spirt playing on MTV 5x a day along with the Chili Peppers, Under The Bridge and Right Said Fred, I'm too Sexy For My Shirt 😂 to Seal's hit Kiss from a Rose and the heartbreaking Clapton's Tears in Heaven. How did the time go by so fast? Remember Mathew Sweet, Girlfriend? That song was on MTV every day, then disappeared.

[@zhiyucui8343]

I am diagnosed with type 2 diabetes so I am very glad to learn from you a bit about the process our body deals with blood sugar and its failure. One question … when insulin cascade process works, glucose gets absorbed into all kinds of cells. Would glucose not damage the cell?

[@SmallBobby]

You may want to consider his two videos on the effects of diabetes on the mitochondrion. kzbin.info/www/bejne/gYKlnqewiZmJirc&t kzbin.info/www/bejne/rmeogJuKr7t-qac He goes into detail on how the glucose and fatty acids are used up in a normal state and how it becomes dysfunctional in a diabetic state. Essentially glucose and fatty acids are fine until there's too much supply and not enough demand.

[@isa-manuelaalbrecht2951]

I expect you to go for muchmore nerdy infos..we need to be intructed...great stuff thanx from Isa healthpractioner in Switzerland ( nutrigenomics...) 😁🤩😏🤗👏👏👏🥰

[@muleface1066]

Some of us, I suspect, will understand all of this (not me). Most of us will understand some of it. And some of us won't understand very much at all. But if we're going to learn anything, we have to be challenged. So I appreciate the detail. These are complex subjects, so even if that's all we get from this, we learn a new appreciation for the scientists.

[@KoiRun50]

Well done. I’ve learned a lot!

[@Physionic]

Great!

[@peterholt4806]

Nic. I love your presentations. Both the detail and your relaxed style. However, and this isn't aimed just at you, I hate the use of the term "Blood sugar". The sugar in blood is Glucose. It is "a sugar" (one of a few ..oses), but it is not what we all know as "sugar". Which is "white stuff". "Table sugar". "Sucrose". I know of quite a few people who have had reports of raised "Blood sugar" and so they have cut down on "sugar", but still continued with high levels of Starch, not realising that it is refined Starch that, more than anything else, raises your blood glucose. It would be more beneficial for population education if you all called it "Blood Starch". I know that Sucrose has its issues in the body, and for intake to be reduced, but for most people with blood glucose issues, your best bet is to give up anything with wheat in, as well as Sucrose.

[@Constantine-the-Great2000]

Good afternoon Mr. Verhoeven and thank you for your good work!

[@Physionic]

Hi CJ - thank you!

[@jasonhowarth6789]

I enjoy the more in-depth videos. I knew what you were talking about when you said that you wanted calcium for polarity within the mitochondria from a previous video where you described the elctron transfer chain by helping to push the positive protons to the other side of the membrane and then allowing the proton to go back into the last protein back to the other side of the membrane. I think I got that right?!?😅

[@joannawieczorekmd]

I love your work 👏👏👏

[@certifiedhoarder]

I am troubleshooting a broken metabolism in a loved one going on 3 years now. Many many problems accelerating at an alarming rate. Mitochondrial dysfunction seems to tie all symptoms together. 99% insulin resistant score even on ketogenic diet with extended water only fasting (1-3 day) Will whole genome sequencing pinpoint the source of this issue before i run out of time with her? The conventional medical system already got all our money.

[@janinademetriou-warburton6427]

I wish you success with your research. ❤

[@Ferofero8]

🤔 Does a good antioxidant supplement like Vit E, C, Astaxantine, etc could help ti boost sirtuins expression ?

[@KamranConsultant4Hire]

oh shit! you mentioned David Sinclair! He was on my list of questions I have for you sir! Awesome, looking forward to see you investigate his work. PS: BTW you said "we will be discussting the..." 😆

[@Physionic]

Yes, I have a spotlight video I planned on making several months back but never got around to it, maybe I'll record it and do it anyway. Thanks, Kamran.

[@meikhor6212]

Awesome detail explanation! I love it. Thank you so much

[@Physionic]

Glad it was helpful!

[@Amun92]

Can you explain more about the mtDNA acetylation and de-acetylation please

[@privateerburrows]

Amply enjoyed the longer format than what the attention deficient crowds might prefer. I once heard someone say that insuline resistance was manifested as a gradual decrease of the number of insuline receptors on the cell membrane. Is that entirely misguided?, or is it one of the many details you left out?

[@cramireg]

Could you make a video to explain in more detail how sugar molecules in blood cause inflammation in different tissues? You just did big jumps in this video. Thanks.

[@michaelberman3648]

Can you please explain the exact mechanism of how one can develop insulin resistance from just high cortisol levels or high stress levels even though one eats very low amounts of refined carbohydrates and eats good fats and some protein. Can you please explain how a fatty liver can develop anyway???

[@GeorgeFinan-hc8fu]

Please, what are the side effects of sirtuins if. taken orally? Is. It advisable taking it with the meal or before the meal? Thanks

[@adriansrfr]

How does the Randle cycle fit into this? It seems to be critically relevant.

[@GRobLewis]

Great info, thank you. In this and probably other videos, an important question is: when ingested orally, do any of these agents ever find their way into the cells? I guess this is called "bioavailability" and I'd love to hear more about it.

[@WholeCosmos]

you will be disgusting? LOL I know what you meant but still a funny tongue slip. keep up the great videos. There are so many quack DRs on you tube but you are legit.

[@nadineevans2647]

Love your content

[@cholman57]

so you never did say what we can do to create more sirtuins to fight off insulin

[@theursulus]

Hi, I have a question regarding insulin resistance. So, your video outlines the mechanism, nicely done by the way, by which too much glucose/fat creates and over abundance of ROS which in turn can add the incorrect phosphate group to the insulin messenger within the cell. Why doesn't lowering glucose availability fix this. Theoretically if a cell is insulin resistant because of a surplus if ROS then shouldn't simply lowering glucose availability fix this and effectively reset the system? Why is it so hard to reverse insulin resistance? There must be more to it? Or a fast should reset the system at which time glucose metabolism should return to normal.

[@LTPottenger]

Looking forward to this one. And thanks for reminder to take my olive oil!

[@Physionic]

Haha, not sure how that reminder came up, but I'm glad I could help.

[@LTPottenger]

It's a sirtuin activator

[@christian.adriano]

Fantastic 🎉

[@adriansrfr]

Saying that the mitochondria make reactive oxygen species is the same as saying that it makes free radicals.

[@Rocky7729]

This explains how COVID or other infections causes mitochondrial dysfunction leading to increased ROS or insulin resistance and increased DNA mutations or cancer.

[@bjai2607]

Very detail explanation. Definitely take times to digest but what more i could ask for. 👍

[@MARTINJSHERMAN]

Pretty much a waste of time if you are not a graduate, PhD level student. Not only in the weeds, but wandering aimlessly.

[@Physionic]

I am a graduate, PhD level student. Also, why have you been subscribed for 5 months and just now levying this criticism?

[@natalias1212]

Hypoglycemia is low sugar, hyper is high sugar level there is a mistake around min30.

[@Merzui-kg8ds]

So, how does a human sustain the health of their sirtuins?

[@melt7891]

Thanks Nick

[@Physionic]

Thank you, Mel!

[@GregariousAntithesis]

I have heard this description more or less detailed and it always seems like pure theory or hypothesis but not proven. I say this because we know betweem the liver and muscle cells we have roughly 600 grams of glycogen/glucose storage. If someone is habitually consuming a high glycemic diet there glycogen storage will always be full. So then the liver has to convert the extra glucose from a meal into triglycerides in order to keep the blood glucose levels in a normal range. So type 2 diabetes isnt a glucose storage issue its a fat storage and liver, mitocondrial dysfunction issue from damage from ectopic fat causing liver disease and dysfunction and obviously mitocondrial dysfunction. Its from habitual flooding the liver with pure fuel sugar and fat primarily from processed food but animal products can be contributory. Processed food is like pure fuel in a whole food digestive system. If it were whole foods animal and plant it would be far harder to cause flooding of fuel because of fiber and how meat is comprised its slower and more evenly digested.

[@alexandervaldez582]

If sirtuins act in deacetylation in the mitochondria, could they have the same effect as ketone bodies in the cardiomyocyte?

[@Physionic]

They could - it depends on if the acetylation is accessible to the enzyme. I think I covered a bit on ketones and sirtuins in my "ketones cause heart damage" video discussing the mechanism, specifically.

[@alexandervaldez582]

@@Physionic ok, thanks.

[@jaredhouston4223]

Superoxide is innately found in the mitochondria, so I should take this information as something the body creates on it's own? We make our own antioxidants or are there more functions for superoxide? Glycosylase is reading and fixing errors in genes, what are it's components and how do we help this system? If errors happen 1 out of 100 million times should we consider that cancers are a result of a poorly functioning Glycosylase system, perhaps the body is not receiving the correct nutrition an over abundance of poor nutrition that just adds more stress to the already poorly functioning system. How do these systems perform during fasting, during high energy intake, low energy intake over LONG periods of time and will different foods create different components of these systems, specifically Glycosylase? Sirtuins sound like messengers in a cell, is that their role in a nutshell?

[@Physionic]

The body generates its own superoxide (this is a ROS), and it generates its own superoxide dismutase (the antioxidant). The components of glycosylase are amino acids, just like any other enzyme. I think the only way to help it is by leading a healthy lifestyle and avoiding cancer causing habits (sun with no sunscreen, for example). Fasting and low energy intake tend to slow the damaging of our cells, but I'm unsure how it would necessarily affect our repair systems - I don't think it's been studied. In a manner of speaking, sure, but that's true of many proteins in our cells (messengers).

[@jaredhouston4223]

@@Physionic Thank you for answering all my questions. I know nothing about this biology, lots of interactions going on very complex.

[@lynnwilliams5432]

Increase sirtuins with sardines and fish oil Omega3 so he said in another podcast. Beware degradation of shelved fish oils.

[@davethe-bear9923]

NERD ON!!!

[@StephenHutchison]

It looks like you're not promoting the "life extension/aging reduction" side of these chemicals. Given that the initial research was snapped up by Glaxo-Kline (along with the company that did the initial research) in a highly publicized explosion of propaganda and pre-sales, only for later, and commercially suppressed, researchers who found that the original research was full of fluorescence artifacts ... anyway. Yeah. Can you identify more (as time allows of course) of the actual not-invalidated not-tainted research that actually does make these proteins useful?

[@amyamy5242]

Can i kindly get your email id? I have few queries on mitochondria's connection to diabetes.

[@zhiyucui8343]

I am diagnosed with type 2 diabetes so I am very glad to learn from you a bit about the process our body deals with blood sugar and its failure. One question … when insulin cascade process works, glucose gets absorbed into all kinds of cells. Would glucose not damage the cell?