5 Mechanisms of Anti-Aging, Science Explained.

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[1] Mohammed I, Hollenberg MD, Ding H, Triggle CR. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Front Endocrinol (Lausanne). 2021;12:718942. Published 2021 Aug 5. doi:10.3389/fendo.2021.718942
[2] Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z. Epub 2017 Aug 3. PMID: 28776086; PMCID: PMC5552828.
[3] Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121-135. doi:10.1038/nrm.2017.95
[4] Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392-395. doi:10.1038/nature08221
[5] Selvarani R, Mohammed S, Richardson A. Effect of rapamycin on aging and age-related diseases-past and future. Geroscience. 2021;43(3):1135-1158. doi:10.1007/s11357-020-00274-1
[6] Ehninger D, Neff F, Xie K. Longevity, aging and rapamycin. Cell Mol Life Sci. 2014;71(22):4325-4346. doi:10.1007/s00018-014-1677-1
[7] Ehninger D, Neff F, Xie K. Longevity, aging and rapamycin. Cell Mol Life Sci. 2014;71(22):4325-4346. doi:10.1007/s00018-014-1677-1
[8] Dorling JL, Martin CK, Redman LM. Calorie restriction for enhanced longevity: The role of novel dietary strategies in the present obesogenic environment. Ageing Res Rev. 2020;64:101038. doi:10.1016/j.arr.2020.101038
[9] Zia A, Farkhondeh T, Pourbagher-Shahri AM, Samarghandian S. The role of curcumin in aging and senescence: Molecular mechanisms. Biomed Pharmacother. 2021;134:111119. doi:10.1016/j.biopha.2020.111119
[10] Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246-1256. doi:10.1038/s41591-018-0092-9
[11] Kowald A, Kirkwood TBL. Senolytics and the compression of late-life mortality. Exp Gerontol. 2021;155:111588. doi:10.1016/j.exger.2021.111588
[12] Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28. doi:10.1016/j.ebiom.2018.09.015
#antiaging #antiagingtreatment #agingbackwards
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18 сен 2024

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Комментарии : 129

@ahrmiller2003 7 месяцев назад

Great content, analysis, and humor. Thank you.

@keng7758 Год назад

You have a very engaging, informative content, voice and style. Great channel! Btw, based on a new video from Dr. Brad Stanfield, I’m dropping Metformin but will continue with Berberine to lower my slightly elevated blood glucose level. I had talked my doctor into prescribing Metformin but she was right. I don’t need it and the impact it had on exercise performance and testosterone helped me decide to drop it. Good look to you!

@Physionic Год назад

Kind of you, Ken. Thank you. I need to re-investigate metformin. I appreciate you sharing - thank you!

@deborahhall9744 7 месяцев назад

When you investigate Metformin please also investigate Berberine -- it has some adverse effects too. A comparison of the two with pros and cons would be helpful@@Physionic

@triatct Год назад

At 63 I am very interested in a longer lifespan! At least staying healthy and active as long as possible. I just recently became obsessed with healthy lifestyle. I have been doing keto for 3 years and lost 60 pounds. I guess that's calorie restriction! I have tried different vitamins and minerals as an experiment. None seem to be noticeable to me but Ir recently since starting GLYNAC supplements and have noticed better sleep and wake up feeling clear headed and more alert. Hope that continues.

@Physionic Год назад

I've been really interested in your experience with GlyNAC - that seems to fit the data from the study analysis I did (I think you shared your experience there, too). Thanks for sharing!

@sarahzwolle4107 Год назад

Thank you for the info, quick question, could I take glycine with nac, if so how much? Have a blessed weekend!

@triatct Год назад

@@sarahzwolle4107 I take a powder that has both at 1800mg and some taurine in the evening

@robgibb430 3 месяца назад

What kind of fat is the basis of your keto diet for longevity?

@triatct 3 месяца назад

@@robgibb430 I use very little added fat. Some olive oil and a little butter. Mostly just the fat that comes in meats. I do eat a little dairy. Mostly full fat cheeses

@K_F_fox Год назад

After I lost a good deal of weight, even though my BMI was in excess of 26, I started experiencing skinny shaming and loss of friendships due to my insistence on maintaining the practice of "energy restriction." I'm wondering if using that branding, actually saying "energy restriction" instead of "caloric restriction" does help avoid triggering people. I've recently been told that describing my diet to doctors as "a euglycemic diet" will make my life much easier than calling it "ketogenic" or "high fat/low carb," but I haven't had the chance to try that yet.

@Physionic Год назад

Tell 'em to kick rocks, Kaiden. Congratulations on your success - you deserve every praise. Creative way to get around it, though - 'euglycemic diet', haha - I like it!

@ciaranryan7303 Год назад

Barberine has been shown to be as effective at controlling blood sugar as methformin and also activates AMPK so could be a good alternative especially as in most countries methformin is only available on prescription. "Aging associated decline in intrinsic capacity" has been classed as a disease by WHO but I imagine my doctor would need a lot of convincing. 😅

@susymay7831 Год назад

Hidden gem channel! 💎

@Physionic Год назад

Thank you, Susy.

@fsero Год назад

I am mostly concerned with increasing healthspan. I am 61 and still work as a surgical tech. Have to be fast, strong and work 12 to 16 hour shifts. Thank you for your videos. I hope to omprove me gait stability and speed. Also grip strength. Much appreciated!

@Santa-ny1yp Год назад

With senolytics, there are many. They go after different senescent cells and last different amount of times in the system.

@Gwalothel Год назад

Very interesting. Have you also read about alpha-Ketoglutarate? I‘d like to hear your opinion on it.

@sooooooooDark Год назад

i once read some sciency paper and noticed (it wasnt explicitly mentioned in the paper actually, i felt smart for noticing it 😂) that caloricly restricted (i think it was) rats (or mice?) indeed hat significantly longer lifespans however one caveat: the variance in their lifespan was MUCH larger

@Physionic Год назад

That's fascinating. I wonder why there was so much difference between animals. Maybe just a small sample size?

@tonyprice2256 Год назад

I will live as long as i can by consuming natural real foods. I am currently 66 and use absolutely no pharmaceutical products - prescribed or over the counter for any reason whatsoever. I also see no need to visit any medical doctors anytime soon at least. None of them have ever helped me reverse any of the chronic health conditions i used to have for decades, and none of them have a clue regarding basic nutrition. They are not trained to heal anything. They are only trained to manage and 'treat' chronic health conditions with pharmaceutical solutions. That is not good enough in my opinion.

@Leto2ndAtreides 7 месяцев назад

It’s true that most are specialized. So sometimes you need to do your own research and then find the right type. I think we’re 20-ish years from fairly good age reversal tech… Would be sad to die before having a chance to be young again.

@glorytoukraine619 11 дней назад

If you live in North America, you have to take all these supplements and vitamins to really eat close to "natural." Unfortunately, the food there lacks a huge amount of nutrients, unlike in Europe.

@JonasGaida Год назад

This is an insanely well-done video!

@Physionic Год назад

Kind of you, Jonas - thank you.

@homesignup Год назад

Super! Thanks so much for the major anti-aging summary and mechanisms and love the pics!! Metformin is the only one I would take out because newer studies appear to show it doesn't extend lifespan in humans (though it appears to extend lifespan in yeast, worms, mice). It's great for diabetics though. I prefer berberine. I definitely do believe in calorie/energy restriction though. Fab video!🤩

@Physionic Год назад

I’ll have to look into it, then. Thanks for bringing it on my radar, Talia. As always. :)

@keng7758 Год назад

@@Physionic Agree that Metformin is now regarded as not recommended unless you have diabetes or pre-diabetes. Per Dr. Brad Stanfields RU-vid channel today, Metformin has been shown to reduce the effectiveness of exercise (particularly VO2 Max) and also seems to decrease testosterone. I had asked my Dr. to prescribe it and she did as I’m slightly over the line towards pre diabetes but now I’m stopping it as I now exercise regularly and will take Berberine instead. Great channel!

@keng7758 Год назад

@@Krunch2020 Dr. Brad Stanfield is a legitimate MD in New Zealand. He also spends a great deal of his time to read published papers on the effectiveness of various medications and supplements. As he has said that he prescribes Metformin to his diabetic patients. That said, he also comments on the drawbacks of Metformin. Metformin is dirt cheap (so there is no profit in It for Pharma) so there are no large scale human studies that are currently being done on it for longevity purposes. Check your facts before you spout off please.

@jan-ck7td Год назад

@@keng7758 what about TAME?

@keng7758 Год назад

@@jan-ck7td TAME? definition please

@heidih3048 Год назад

metformin impaired my father's kidney function seriously as he used it for over 5 years. His kidney function is now restored after being off metformin for several months.

@alchinov4695 Год назад

Awesome video, very informative! I was wondering when will you cover some natural foods, drinks and supplements that have an anti-aging effect, increasing autophagy and stem cells, like (black) coffee, green tea (egcg), dark chocolate (theobromine), red wine and blueberries (resveratrol), broccoli sprouts (sulforophane), moringa leaf (myrosinase), turmeric (curcumin) etc.?

@Physionic Год назад

So much to cover, so little time. :) I’m trudging through each topic as fast as I can, but I will, Alchinov, thanks!

@alchinov4695 Год назад

@@Physionic hahah thanks for the feedback, I am eagerly waiting for your upcoming videos. I love your content and have binge-watched your videos these past few days. Keep up the hard work!

@Sousaquasesosia Год назад

Fantastic video, Nic! By the way, on "natural remedies" to senescence cells, I've seen this article recently that you may be interested (in case you haven't checked it yet). It argues that a substance in grape seeds is even more potent than Fisetin (a summary is extended data/fig. 1).

@Physionic Год назад

That would be wonderful, Paulo. If you can send me a message or tag me if you post it in the community, I'll check it out - thanks!

@Sousaquasesosia Год назад

@@Physionic Oh I see that the link to the article that I posted here was not uploaded. I will try to post the link in the community.

@Sam-shushu Год назад

Awesome channel. This is exactly the sort of stuff I'm into. I'm glad you looked so in depth into these, I don't have a microbiology background and it's been years piecing things together in my own as I read studies. This helps correct a lot of my misinterpretations and mistaken understandings.

@Physionic Год назад

Thanks, Sam!

@erikjanse3994 Год назад

Thanks for the VDO and the excellent presentation. Would be nice to hear what mechanisme you choose to use for yourself! Thanks!!

@bingandrew3266 Год назад

This is one of the best explanation. Great job!

@filipinoblackpill6194 Год назад

Keto is calorie restriction, intermitent fasting is also calorie restriction. Keto is not healthy long term. I suspect it can damage your internal organs.

@Vogeln Год назад

I've been both eating turmeric, combined with black pepper, for years, and taking turmeric capsules with piperin for several months. I've been doing this because I heard, years ago, that curcumin was a powerful anti-cancer, neuro-protective (anti-Alzheimer's), has a powerful anti-inflammatory properties and now, also a senolytic. Is fisatin as mutifaceted as curcumin?

@kedabro1957 Год назад

Piperine tears holes in your gut.

@Leto2ndAtreides 7 месяцев назад

I tried Fisetin + Quercetin. It did seem to improve my skin for a while but that was as far as I could tell in terms of obvious results. It also suffers from being difficult to absorb unless it’s in a fat absorbed form or something. Quercetin + Dasatinib probably also deserves more attention… I assume that there have been more studies.

@Burnrate Год назад

have you ever checked out tryptophan? Would be super interesting to get your take on that

@RosenetTV Год назад

Hi there. First and foremost, very interesting content on your channel, you've drawn me in! Question about Berberine compared to Metformin. Dr. Sinclair has noted that Berberine works similarly to Metformin. I cannot get Metformin here with out a prescription, so I am taking Berberine instead. Any insights on Berberine in this context? Also plan to try the glyNAC combo starting this month.

@fabianschneider3677 11 месяцев назад

I love that one: 2:03 😀

@quickcube2834 Год назад

I thought that most senescent Cells are senescent because there Epigenome has changed to a point they not function like they should or they run out of telomeres.

@Physionic Год назад

You’re right. They reprogram through the epigenome changes. The genome itself doesn’t change.

@matthewatdefiantlegends7629 Год назад

Great video, as always! I would love to hear your thoughts on medicinal mushrooms like Lions Mane. Cheers!

@rtnjo6936 Год назад

Once again, awesome video! Glad I turned on notifications for all your videos!

@Physionic Год назад

Thank you, RTN! I appreciate it.

@glorytoukraine619 11 дней назад

If you live in North America, you have to take all these supplements and vitamins to really eat close to "natural." Unfortunately, the food there lacks a huge amount of nutrients, unlike in Europe.

@creativesource3514 Год назад

I'm 103. I'm interested in.....arrrggh! Chest pain!😵

@richardcottone6620 Год назад

I'd like you to resurch the effects of thalassemia minor on aging. possibly with a constant red blood count of between 8.5 and 10. maybe inhibiting cell production

@edthoreum7625 Год назад

6:25 rapamycin

@pjaworek6793 Год назад

Awesome, you rock Nic!

@Physionic Год назад

Thanks, P! :)

@gloriamitchell4005 11 месяцев назад

Wonderful!

@FoxGhost7 Год назад

Okay, I have a difficult question: from my research, it seems Creatine upregulates both mTor and AMPK. Isn't that at oddes with each other? Also seems to decrease blood sugar levels and other stuff. Could belong on this list?

@donaldhenderson1870 Год назад

I take rapamycin but it does increase glyconucleogenisis. My blood glucose goes up around 10 mg/dL after taking rapamycin for several days. Its half life in your body is about 4 days and should only be taken every 10-14 days. Unfortunately, the FDA makes it hard to get. Metformin has failed thus far to extend lifespan in human studies and leads to decreases in muscle mass and aerobic performance. It also upsets my stomach something terribly. If you take rapamycin you don’t need chronic caloric restriction, however cycling between excess and deficiency on a daily of weekly basis will delivers the benefits of AMPK.

@BillyRubinIII Год назад

I'm interested in Rapa, I have ME/CFS and heard it can help, have you noticed any increase in energy? Am worried about sides like mouth ulcers (I already suffer with them) or loss of muscle mass? How long have you been taking it?

@eddiesmith7867 3 дня назад

Brother where you get that stuff

@sachli 4 месяца назад

How about NMN?

@chuckkolb1270 Год назад

thorough, clear and a bit of fun

@Physionic Год назад

Thanks, Chuck!

@jasonchu852 Год назад

very interesting !

@faithwhite3175 6 дней назад

What is VovO,?

@emanuelzbeda1420 Год назад

Love the born in 1467 bit. Anti-aging properties of vampiricism next??

@Physionic Год назад

We're getting there... :)

@LTPottenger Год назад

Taking berberine, which is what metformin is based on, completely screwed up my gut and it has only gotten better slowly and for a long time not at all.

@Physionic Год назад

That's a real shame, PH. How did it screw it up?

@almaramirez7365 Год назад

I just started taking it, how did it screw up your gut?

@johnspain8714 11 месяцев назад

So is curcumin like... the spice?

@bill9989 Год назад

I have a very basic question: I am 74 years old (yikes!!!!), non diabetic male, and have been taking metformin for almost 2 years. However, given that metformin harms or perhaps stresses the mitochondria, am I too old for it? Is my mitochondria too old and infirm to tolerate and improve from that induced stress?

@tomblalock 5 месяцев назад

CD38 increases with rising luteinizing hormone

@karenf9137 Год назад

An April interview with Dr. Paul Saladino and Georgi Dinkov touched on this topic. In short, they contradict everything here, even fasting. Ugh! I’m confused.

@Vogeln Год назад

Can you please explain the seemingly dependent relationship between mTOR and Rapamycin? Since the "TOR" in mTOR stands for "Target Of Rapamycin", it seems logical that Rapamycin was discovered first and that the only thing known about mTOR is that it is Rapamycin's complement. Are both of my assumptions wrong or simplistic?

@alyousuf Год назад

Apparently Sulforaphane is a much more potent activator of the NRF2 pathway

@darcyfernandes8922 Год назад

Good.

@Beans-great Год назад

What are your thoughts on GlyNAC?

@Physionic Год назад

I have a lengthy video on it.

@Physionic Год назад

ru-vid.com/video/%D0%B2%D0%B8%D0%B4%D0%B5%D0%BE-6Lmc-mmqxyQ.html

@Beans-great Год назад

My memory needs a bit of a workout as the previous video I watched from you was that exact data breakdown lol. Which was excellent by the way. Enjoying your content!

@Physionic Год назад

Thanks, Sean!

@zer0thzero428 Год назад

Note that Metformin has been found to deplete B12 levels over time. Personally I consume foods rich in B12 to counteract that effect... e.g. sardines.

@N330AA Год назад

Also reduces Testosterone, so Berberine is touted as superior.

@Aki-wq6xh Год назад

It really hurts me after three months. I still have hundreds at home but decided to ditch it and go to Berberine

@filipinoblackpill6194 Год назад

Metformin can increase creatinine and impair your kidneys

@filipinoblackpill6194 Год назад

Is saturated fat from butter healthy to eat everyday. Also what is the most healthy diet for long term.

@robgibb430 3 месяца назад

No. Wfpb

@jennaz9790 Год назад

You’re intelligent af 😊

@Physionic Год назад

Thanks, Jenna - I have much to learn, still, though. :)

@robertrowan9893 Год назад

All in all, it got me thinking about those who age at a pronounced rate, I seem to remember being pro... The name eludes me. Where do they figure in all this? And those grapeseed complex capsules that I refrained from purchasing this afternoon. They've got some good press associated with them. I hope they're on what we Brits term short date - ready to be discounted before too long. All health food - food for thought.

@aljosarojac8575 Год назад

Hi Physionic, it is a very nice video, but I could not understand your dispute about calories and energy. Calories are/is energy. So energy restriction is calorie restriction. Why do you avoid the c-word?

@Physionic Год назад

Many people just don’t believe in calories. I was just poking fun at that crowd. :)

@aljosarojac8575 Год назад

@@Physionic Gotcha 👍😃 thank you.

@filipinoblackpill6194 Год назад

I can attest this. My whole life im on calorie restriction. Im weak no energy and gets cold all the time.

@lorrains.robinson1404 Год назад

I already take curcumin pills, what would happen if I mix it with metformin?

@dr.julia-heyakarcic8862 11 месяцев назад

Fasting triggers autophagy, fasting is the fountain of youth

@colorme6536 Год назад

How old r u and do u fast or use supplements and what is your exercise routine

@faithwhite3175 6 дней назад

Fox I?

@seranonable Год назад

On Dr Stanfield's channel he had Dr. Miller of Interventions Testing on who touted with great authority that they tested various senolytics (including fisetin) and found no effect. I can't help but get a greasy vibe off of the man but I know that doesn't necessarily make him wrong, but I'm curious if you had any thoughts on what he presents. I'm sure I could dig up the link if you'd like.

@Physionic Год назад

Honestly, I need to look into fisetin far more. I hope to do so soon. If you can find the link, please do - although, if you send it via RU-vid, it may get autodeleted (not by me, by RU-vid).

@seranonable Год назад

@@Physionic Okay so since the link won't work, the video is called "Stop Quercetin Now (New Study)" it's from May 15, 2022 also I was misremembering him having Dr. Miller on his show, he actually references a clip of Dr. Miller on another person's show... but the content of the discussion is the same

@johntanaka131 Год назад

How much doses of metformin can we take for its longetivy effect works? Thanks

@keng7758 Год назад

I’ve been taking it at 1000mg for a few months but I’m stopping as of today based on the latest study results posted by Dr. Brad Stanfield. It has no longevity benefit based on the latest studies and decreases exercise benefits and decreases testosterone. I really do t need it for my slightly elevated blood glucose so I’ll use Berberine instead. Good luck to you!

@miracoli16 Год назад

Zero

@mjordan5382 Год назад

You has me at C C Calories 😂 I honestly feel like Calories don't apply to the human body. Calories are made when you light something on fire and measure the pure heat output. And the body instead uses mass and chemical energy from food....not Calories aka heat energy...

@Physionic Год назад

Hehe, well, maybe I can change your mind when I release my video explaining the biochemistry of calories. :)

@mjordan5382 Год назад

@@Physionic alright cool

@ZappyOh Год назад

Humanity needs a new universal law: Nobody is permitted to live past 100 years. ... I mean with all this research in life extension, we will never escape a handful of old rich guys ruling the World.

@tonyprice2256 Год назад

We will never escape the handful of rich guys that rule the world. It has been this way for thousands of years. The masses are simply too lazy, complacent and ignorant to rebel. And there have been people who have lived in excess of 100 years who did not rule the world.

@noneofurbusiness5223 Год назад

Also, I definitely want quality of life. Sleeping 22/24 hrs is no life.

@noneofurbusiness5223 Год назад

I had a *very* embarrassing episode because of Metformin. Was on it for 20 yrs - can't tolerate it @ all.

@noneofurbusiness5223 Год назад

Thanks either phone 📱 or RU-vid won't let me give you thumbs 👍

@eddyskipper2743 Год назад

most people i tell about Bryan Johnsons Blueprint just reply that they'd rather die gray and old. people dont have any drive to pursue optimal living on this planet, people are just lazy. so your assumption about most people being interested in age reversal i probably wrong

@arihaviv8510 6 месяцев назад

But that also means ending up in the hospital often with painful conditions (diabetes, Alzheimer's etc) years before dying. Or even just living off all these medications. Why would they want that

@eddyskipper2743 6 месяцев назад

@@arihaviv8510 because it's easy. people are stupid ask around most people don't even believe supplements have an effect. they are workers trained to work and not ask qustions. ask around you. i tell you most people are walking cadavrs at this point.

@FinTra_ Год назад

So does this mean that when you increase energy production with calorie dense molecule such a sugar, you increase aging by promoting cell division hece early senescene. So ideal would be calorie light foods that have other molecules that promote repair and have an abundance of building blocks for repair. Vegan? 😂😂😂

@jamesbyrne9312 Год назад

Sick of hearing about metformin. No one can afford it

@filipinoblackpill6194 Год назад

Sub

@shawnlewis1918 Год назад

NOPE...I'll take a HUGE pass on synthetic man made drugs! True anti aging benefits are optimal through natural foods and fasting along with supplementing with a quality collagen for cell regeneration and without the typical pharmaceutical side effects eventually!