A Longevity Breakthrough w/ Yamanaka Factor "Rejuvenation Cocktail?" | 53 - Longevity Reacts #3

[@steveholmes1736]

Matt is so frank and point-blank. This makes him entirely and completely believable. This was a great show. Sometime ago I did a literature search involving this very subject. I wanted to know what happened when old organs were transplanted into young recipients and vice versa. It was very very difficult to get information on this. I’d still like to know very much more. Thanks for the great program!

[@optispan]

Thanks! We do have a previous episode about parabiosis (in this case young blood put into old rats): kzbin.info/www/bejne/n6ezZISKrrZlmpY. But we will consider delving more into this topic based on your feedback. - Tara

[@jimfife6255]

I was 61 when I got a 39-y.o. new liver. Go Team! (taking Rapamune, for my I.S., too)

[@joshlocher71]

@@optispan i thought this was david sinclair's cocktail

[@brendanvanderes6605]

Have you all looked into the new nature article on anti-IL11 therapy's impact on healthspan? Would be an interesting deep-dive..

[@renliu35]

Hey Matt, I’m 30 years old and i wanted to thank you for all this great knowledge. Cheers!

[@catorepublic]

Thank you for this talk. There is another key moment in the Aspen Institute panel at minute 39 where Klausner says they can take old animals and reprogram them to rejuvenate just the muscle fibers. He says those animals are "profoundly more healthy metabolically." They lose fat and they benefit from the signaling molecules from muscle, including myokines and exerkines.

[@askingwhy123]

Another great video. It's very positive to see competent scientists addressing aging.

[@edgarwilhelm8055]

Thank you again as always for the time you spend to discuss this panel. I really appreciate the insightful comments of Mat Kaeberlein! Looking forward to your next broadcast!!!

[@opensocietyenjoyer]

this is 100% a bot

[@optispan]

Glad you enjoyed it!

[@workingTchr]

"The rejuvenation cocktail". Just hearing that phrase uttered seriously is something.

[@jonathonmills3563]

The only two “supplements “ that reached statistical significance in the NIH ITP trials are Glycine and Astaxanthin.

[@metaphysicalArtist]

Glycine and Astaxanthin mg dosage per kilo ?

[@opensocietyenjoyer]

i hate this "statistical significance" nonsense. if something is stat. significant but you have no theory explaining how that could be your study alone is useless.

[@JB-jg9lo]

@@metaphysicalArtistastaxantin dosage was 4000 ppm, after re-calculate for human equivalent dose it is about 46 mg/kg/day; Glycine was 1,6 mg/g of feed; as far as I remember asta was not tested in ITP

[@JB-jg9lo]

More than these was tested sucessufully, luckily

[@greghoscheit7896]

@@metaphysicalArtist

[@newyorkskier]

I don't think NAD precursors have been claimed to increase lifespan except in some specific health background. What NAD precursors have shown is improvement in some markers of health.

[@myqp12345]

Epigenetic reprogramming is is THE KEY intervention to cellular aging. A partial reset of methylation so specialized cell is reset to its initial state but not to stem cell state is a big part but so is being able to precisely turn on/off gene expression . Example say methylation has shut off P53 , only reset the methylation that has shut off and the cells can once again use P53 to detect cellular health. Very very powerful with zero off target dirty side effects. I have seen this happen with complex software. A corrupt pointer or memory getting stepped upon and the whole system just shuts down at what appears to be a random event. Finding the problems like this can be tough but the fix is usually simple. Either way you must understand the MOA. So we are at the point where we can understand what went wrong . This is real progress. WAG 5 years from now health care will be very different. Taking supplements is shooting in the dark. Targeting methylation errors is clean and effective. Of course you still have actual snp issues which can also be solved but is a much more complex fix. We all want the good versions of genes but the process of modifying snp's in the same place on all cells is a much harder fix. If I could make that call when I was a single cell I would say yeah go for it!

[@SilverFan21k]

Yall pumping out lots of content

[@nicholasarapis]

We aim for 2 new episodes a week. With the goal in mind of keeping the quality high.

[@davidderidder2667]

Good content.

[@davidwoods1622]

The best possible explanation is that the mice are running out of stem cells. Treatment that target the Hamanaka factors only target 3 of the 4. Targeting all four causes the cells to return to a stem cell state which is uncontrollable in the organism a.k.a cancerous.

[@RyanSturtevant]

Great conversation! There is so much excitement on the internet for the Yamanaka factors reversing aging or at least providing a path to rejuvenate organs. You see Sinclair everywhere. I want to believe, but he is on podcasts talking about it all the time. It’s kind of a red flag, like he wants to sell me something. Hope you do more on the Yamanaka factors. I trust your content. I can watch all the content you can produce on the Yamanaka factors and the corresponding approaches to cell rejuvenation.

[@FatherGorgony]

Idle chatter around Yamanaka. Every third experiment ended with cancer renewal

[@squamish4244]

@@FatherGorgony And yet, if Matt Kaeberlein is seriously talking about it, I don't consider it idle chatter.

[@peterz53]

Interestingly, one of the YFs, OCT4, is upregulated by the ketone body BHB which goes up with fasting and TRE (and exercise). I think Valter Longo showed upregulation of SOX2 by fasting. Also, I have seen literature which shows the apigenin and luteolin upregulate OCT4 and SOX2 in human periodontal ligament cells. Be interesting to screen for these compounds effects on other tissues to verify their efficacy, especially in the context of mild fasting which raises OCT4 (and maybe SOX2). Pure speculation, but there may be a case for periodic mild fasting with a low calories diet high in certain natural compounds which boost expression of YFs.

[@jimfife6255]

Another side effect to consider in the Y-Factor kidney bath, is whether adaptive immune system signaling is epigenetically changed. If the refreshed organ has altered MHC proteins, or in some other way elicits less T-cells response, or less need for immunosuppression, well, that all sounds more healthy.

[@vince1229]

Mouse trials. Like Dr. David Sinclair's longevity and Sirtuins in happy worms.

[@anthonyhopper7830]

A speculative question (layperson): If partial reprogramming doesn't have an anti-cancer effect, wouldn't there be a hard cap (absolute cap) on the mice's lifespans even if they were otherwise fully rejuvenated (assuming they received the cocktail in middle-age/late life when their cancers were already developed)? If that's the case, then partial reprogramming could never radically extend maximum mouse lifespans without an accompanying anti-cancer therapy.

[@reinerheiner1148]

I'd guess that the chance for cancer rises the more cells lose their epigenetic status quo. So if the epigenetic status quo can be reset to a youthful state, then the chance for cancer would be reset to an organism on a youthful state too. At least that would be my guess.

[@rhyothemisprinceps1617]

I read a news article today about an experiment that involved putting planarian genes (JmjC domain-encoding genes) into fruit flies, which "promoted greater intestinal stem cell division, whilst also suppressing intestinal cells that were mis-differentiating, or going wrong in aged flies." It seems strange that these genes could be dragged and dropped from worms into flies with such good results.

[@JohnnyMagorish]

Great video as usual. Would I be correct in assuming the injected mice were not engineered mice? Also, I wonder why this study has not appeared as a paper (even a pre-print), or do you think that’s forthcoming?

[@ghffrsfygdhfjkjiysdz]

The problem with any age reversal research is that no big pharma companies want to pay for it; because patent only lasts 20 years. Big pharma wants to pay for research of how to do heart or kidney transplant better, with less failures. So, the age reversal researchers have to piggyback their research on some sponsored work.

[@livingsmart]

But can you restore elastin or revert RAGEing collagen spikes with epigenetic programming? Because if not - they would need the separate solutions.

[@olyav5819]

Thank you for commenting on the video!

[@ShawnLearn]

Do you believe that caloric restriction is good for health span or just lifespan? Also, is there potentially a negative lifespan impact due to Sarcopenia if the subject is actively using resistance training? I am sure that you know that Dr. Peter Attia mentions this potential conflict with intermittent fasting in his book “Outlive”. Do you think that this issue may also connect to all caloric restriction?

[@invertage]

Lot of variables, different people, different lifestyles, different types of caloric restriction. I do a form of caloric restriction that seems to work well for me.

[@phoneywheeze]

can you make a video on David Sinclair and his Lifespan Book & Podcast

[@Nelis1324]

Could you guys do a video on Irina Conboy’s blood dilution mice experiment? I’d love to know your opinion?

[@medicinefuture]

What about the long lived protein like extracellular matrix, nuclear membrane, do those also reversed, what about mutations in DNA does that also reversed or not

[@cactuscanine3531]

“Be careful of science on KZbin” says the scientist on KZbin.

[@optispan]

It’s a catch 22! But we’re going to do our best to be accurate and a trustworthy source of information - Nick

[@cactuscanine3531]

@@optispan no criticism intended. I just found it funny.

[@JustinPenrose-u4g]

Plasma dilution and young plasma: kzbin.info/www/bejne/foOthXqgjsl9q9k

[@60-Is-The-New-30]

Sorry, Mr. Kaeberlein, exercise is the granddaddy, and everything else is its baby. Everything revolves around exercise. We were born to move, not eat, sleep, or have social connections. When you come out of the womb, YOU MOVE, you don't ask for something to eat. Without a doubt, EXERCISE IS THE MOST IMPORTANT. I can easily prove this with scientific literature. We eat so we can have more energy to move. We don't exercise so we can make it easier to eat. I can go on and on.

[@optispan]

Exercise is extremely beneficial and the most powerful longevity intervention! But it’s hard to rank the 4 pillars since they are all essential to survival. But you can pick a favorite… and it seems both of ours is exercise. - Nick

[@60-Is-The-New-30]

@@optispan Hi Nick. Ok, I will leave you with this. Lack of exercise is a MAJOR AND PRIMARY cause of chronic diseases. You exercise for life and you avoid almost all diseases. I am soon going to publish a video on this specific subject

[@nicholasarapis]

@@60-Is-The-New-30 I’ll keep an eye out for that video. If you’re ever in Seattle Washington I’ll test your grip strength, VO2 max, broad jump, etc at Optispan 💪🏼

[@60-Is-The-New-30]

@@nicholasarapis interesting. I would love that. The results may surprise you😄

[@main___name___main___name]

Cut the crap - is it possible to do programmed epigentic modification or not???

[@seban-jackedweeb5513]

It always makes me cringe when I here questions like, "So mAnY SuPPlEmenTs (or diets), WhAT gOod. sO cOnfuSINg?" It's not a problem of advertising, it's a problem of a lack of basic science literacy, especially understanding basic hierachy of evidence. It's truly insane there's little suspicion from people when they hear mechanistic speculation bs over human outcomes, let alone maybe reading anything beyond just an abstract. I know I should be sympathetic, but something just boils in me when I here things showing a lack of basic science literacy. The vast majority of the time, it's just missing the forest for the trees. In all honesty, the more I read and learn about exercise and fundamental diet principles, like high fiber, high protein, low saturated fat, etc, the less impressed I am with literally anything that isn't a straight up drug, like statins or blood pressure medication (nothing wrong with drugs, by the way. I know the way I said may come off as if I'm against these medications). Hazard ratios comparing the consumption of one food or supplement compared to exercise or body fat or total fiber really puts things into perspective.