Aging By Autodigestion: Geert Schmid-Schöenbein, PhD

[@conqueragingordietrying123]

Timestamps 0:00 Introduction 0:36 Aging By Autodigestion Presentation Q&A 39:22 Only 1 paper on aging and autodigestion? 40:45 Is a high-protein diet driving the aging by autodigestion phenotype? 50:28 Less protease digestive enzyme leak on a methionine-restricted diet? 51:44 Bacterial vs human protease leakage into the blood? 58:02 Minimal protease leak on calorie restriction? 59:30 Is there an optimal window after eating to allow for intestinal repair? 1:02:10 Are there plasma biomarkers of autodigestion? 1:07:05 Could albumin's age-related decline be a sign of autodigestion? 1:07:44 Do anti-trypsin plasma levels decline during aging? 1:09:22 Future studies

[@jimb1580]

Thank you for the timestamps! 😊

[@michaelayalaathotmai]

kzbin.info/www/bejne/rWTJl4BriM-Cr5o Are these lab animals fed on ultra-processed standard lab chow? I suspect what they are eating is a huge factor. Is anyone investigating the hydration state of the animals? Intra-cellular water is probably a much bigger factor. Just drinking is no indicator of water absorption into the cells. It's kind of like working on a car: first check the ground on the battery before changing costly parts. Similarly, what is the water content of mucin? Go figure. Next, and also huge, how much glyphosate remains in the highly processed food they are eating, and what is the quality of the water they are given? I suspect ubiquitous contamination might be a major factor if mucin integrity is in question. I think a big takeaway from viewing the age comparison slides is: do not eat highly processed or ultra-processed food for your whole life. Thanks for the great interview! Mike Ayala

[@ericoshea9382]

This is absolutely fascinating. I’m 38 minutes in. The concept that pancreatic digestive enzymes can enter our bloodstream and then damage our organs and accelerate aging is so interesting.

[@rhyothemisprinceps1617]

I'm only half way through. Lung epithelium also releases both proteases and antiproteases, and dietary antioxidants (e.g., sulforaphane, EGCG) can inhibit proteases - according to Meyer and Jaspers, 2015, 'Respiratory protease/antiprotease balance determines susceptibility to viral infection and can be modified by nutritional antioxidants'

[@arthurcgusmao]

Fascinating. Due to people like these science progresses! Let's conquer aging (or die trying).

[@conqueragingordietrying123]

Definitely, and thanks @arthurcgusmao!

[@aljosarojac8575]

Thank you for inspecting different views, different ideas... Good work 👍 I appreciate it a lot.

[@conqueragingordietrying123]

Thanks @aljosarojac8575!

[@peterz53]

Michael, thanks for bringing Geert on. This is very important information. Many thoughts/questions. making me rethink my daily fasting routine to better optimize gut health, like not drinking black coffee in my TRE window, at least a few days a week. Or shrinking my TRE window and calorie intake down a lot one day a week (6 h FMD) to boost gut health. Testing for lipase in my blood work at various times and so on. Also recall mucin mentioned in the work done by the Sonnenburg lab who work a lot on the microbiome, which goes back to the point of optimizing gut barrier function, so will have to revisit their work.

[@costa768]

Gut permeability is significantly increased post exercise Also interesting case with TUDCA, Fasting modulates microbiota, increasing certain species which converts primary bile acids to secondary BA, one of which belongs to the UDCA group TUDCA has a number of effects even decreasing apoptosis "through reduction of endoplasmic reticulum stress and modulation of the unfolded protein response" Also, check the supplementary data they included The study: "Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice"

[@MichaelMerritt]

Meaning Tudca can help reduce permeability?

[@leadfoot8045]

Thank you Michael for putting on Geert !! 😊

[@conqueragingordietrying123]

Thanks @leadfoot8045!

[@InquilineKea]

Wow this might be another way that dietary restriction CR reduces aging

[@conqueragingordietrying123]

Yep!

[@GaiasFleas]

How do we get the digestive enzymes out of the organs once theyre there? I assume that's the next study we can try on humans, and see if epigenetic age changes.

[@ericoshea9382]

Are the main takeaways then is to chew your food; calorie restriction; and smaller meals (but maybe more to ensure sufficient caloric intake) to allow your gut to recover?

[@conqueragingordietrying123]

Fasting, too...

[@ericoshea9382]

@ thanks!

[@FelixLanzalaco]

and plenty of fibre

[@tatiananikolskaya6991]

Fantastic video! Please continue these podcasts!

[@conqueragingordietrying123]

Thanks @tatiananikolskaya6991, and will do!

[@robertdaymouse3784]

Good video. Perhaps he explained this, and I didn't understand his explanation, but it seems far more likely to me that proteolytic/digestive enzymes in the blood are an adaptive response to aging, not a cause of aging. I don't think he has adequately justified how he arrived at his proposed cause and effect relationship. In other words, I think he is blaming the fire man for the fire.

[@bobbobson4030]

How do you suggest that digestive enzymes in the blood help the organism?

[@monnoo8221]

the data he presented is quite compelling, and he presented a mechanism, not a correlative epidemiological study, for which the fire fighter issue often occurs. It is ilnked to a pathological phenotype, the leaky gut, which is also otherwise known to be a major issue (LPS, bacteria). in terms of evolution, maybe, it is then a mechanism to kill quickly. ??? jokes aside: tryptase/trypsin is a major player in the immune response, and strongly elevated in allergic reactions. yet, as part of the immune response it s also tightly controlled, an several levels, as it is kind of a defense using explosives. So, if it enters the blood from a different source, the immune system gets derailed, also on several levels. ...s I think, the fire fighter analogy does not fit for a large part.

[@robertdaymouse3784]

@@bobbobson4030 They dissolve insoluble proteins like Fibrin from scar tissue. That is why I take Nattokinase and Serrapeptase once a week. kzbin.info/www/bejne/gYG7opmBmah0q8Usi=5rV0IqaEccMxYL74

[@robertdaymouse3784]

@@bobbobson4030 I posted an answer but it is not showing up.

[@monnoo8221]

fascinating!! thanks for digging his up and having Prof Schmid-Schöenbein for this presentation. As a personal anecdote, it makes a lot of sense now that a recent Rota virus infection let me age temporarily to a tremndous extent... It took me 2 months to recover. i was suspecting the leaky gut, but not auto digestion. . You have perfect data to check whether your B1 intake has a significant effect on your biological age, since B1 is crucial in gut health, for our tssues as well as for the bacteria

[@ChessMasterNate]

Every year or two, another way we age is discovered. The last one I remember reading about was the build up of glycerol and glyceraldehyde in the cell. I think that was presented in March 2023. And it would be cool to get Eyleen Jorgelina O’Rourke, PhD on to talk about that. I have not seen any interviews with her, so that would be very interesting. I'd like to know if the enzyme that breaks it down, ADH-1, is reduced because a cell is old, the organism is old, or if it is more like a fuse that just sets a time/energy utilization limit on the life of a cell. I don't care that finding new ways we age does not accommodate "escape velocity" as conveniently. I would far rather have the most accurate picture of all the ways we age out there. And the cool thing about both of these is that they show ways each could be addressed. This digesting thing appears to need dozens of studies to get a more accurate picture of it. The obvious questions I would have would be diet related. Effects of additives, microplastics and other environmental molecular interactions, like the myriad of chemicals. Then there are foods and preparation techniques. Would cooking at a lower temperature be better? What if things are predigested in some way, with or without the neutralizing of those enzymes? He talks about texture. Sounds like we should chew well? What about supplements and drugs? We often just swallow those. Pills and capsules might require a lot to break them down, and then you have more enzymes. It does not seem practical to give the body 2 days between meals to repair. What about having on serious meal every 2 days and the rest of the time eating foods that require little if any enzymes. What about the crazy idea of getting interventions glucose (or maybe drinking glucose) and vitamins for two days and then getting a real meal and then back to the IV, and so on? Of course, there are a ton of cool people to interview. George Church, Liz Parrish...

[@RodeaDrive]

Just watched this for the second time as it really is mind blowing and I feel I missed a bunch the first time. So for practical tips, my takeaways are the following: 1. Eat lots of fiber to help maintain mucin. 2. Cut your calories. 3. Practice fasting (intermittent fasting?). 4. Chew your food well. 5. Eat balanced macros - I.e. don’t eat nutrient poor/calorie dense meals (such as high fat meals) 6. Careful about protein overconsumption? What about taking digestive enzymes? Avoid?

[@dariusszablowski5474]

Thank you for the truly novel perspective. Great video. Thank you. ☺

[@conqueragingordietrying123]

Thanks @dariusszablowski5474!

[@juliahello6673]

I ordered a huge bag of essential amino acids. They taste awful - a mixture of artificial sweetener flavor and bitter. I’ll continue to choke them down, though, since it’s a way of getting protein without my body having to use proteases.

[@Deterministisch]

Nattokinase and Bromelain would be in this case really bad, right? Since both (and or the fragments) are as we know able to pass the barrier into the blood.

[@Battery-kf4vu]

Don't really know but bromelain is a cysteine protease whereas both tryptase and nattokinase are serine proteases. So maybe they don't do the same thing. Nattokinase is linked to lower mortality in studies so who knows, maybe it doesn't do the same thing as tryptase, even if both are serine proteases.

[@juliahello6673]

And papain.

[@Deterministisch]

That's why I'm confused. Probably more research is needed

[@jamesgilmore8192]

This is definitely an interesting idea. Clearly the enzymes aren't where they are supposed to be. The question is how much damage are they actually doing? When the inhibitor is administered, the levels reduced, indicating the enzymes are being cleared, but how? Has there been any human cell line work showing functional decline in different cells when treated with the enzymes, or restoration of function when an inhibitor is introduced? There are obviously many ways to access tissues for human research, but I don't see that being easy to fund without human cell line work on function. As with any good paper, there are more questions than answers...

[@Battery-kf4vu]

Could liposomes be used to have an effect on proteases only when they have leaked through the barrier? The liposome would carry the compound that neutralizes the proteases in their payload.

[@Maple597]

Fascinating- thank you!

[@KJ-um1gq]

Does the doctor think protein shakes would be worse or better than protein from meat in terms of the enzymatic response?

[@timwilliams9100]

Very good conversation if you are a medical professional but way over the head of most people.

[@conqueragingordietrying123]

Thanks @timwilliams9100-within that context, I sometimes re-watch podcasts on astrophysics and quantum physics, and usually understand more with repeated watching...

[@rolivier79]

Really great perspective and insightful. Intuitively makes sense and really link to diet digestion and aging. I wonder if fasting minimizes the intestines production of digestive enzymes

[@conqueragingordietrying123]

Thanks @rolivier79. Then, that raises the question, how long after eating should we fast, for the intestine to recover?

[@kuradev]

@@conqueragingordietrying123 and, consequently, how dynamic is this time-to-recovery in relation to ingested calories, macro/micro-nutrient composition of meal, and similar variables? This is really interesting, and something I would have never thought to take in account. Thank you as always!

[@1509archy]

I’d love to hear more about how supplementing with Akkermansia muciniphila can promote health benefits, especially in diabetes, while also breaking down mucin in the gut. How can these two seemingly contradictory effects coexist, given that a reduced mucous layer might lead to issues like autodigestion?

[@conqueragingordietrying123]

Yep, that's a great point, which is why I'm skeptical about Akkermansia. However, with sufficient SCFAs, the mucin layer shouldn't be degraded, and within that context, Akkermansia may be beneficial...

[@monnoo8221]

see the channel of Guy Daniels about the microbime. highly recommended. There are bacteria that are oppotunistic pathogens... beneficial only if everything is ok, and if some parameter goes wrong, they feed on you, or make the derangement chronic. Daniel's main example : Lactobacillus, which make the gut too acidic

[@gotohellfast]

Taking your whey protein shake, does it activate sufficient saliva to be digested correctly or could it cause an issue?

[@AwesomeFDO789]

There's actually multiple amino acids associated with aging not just methionine, aspartic acid, leucine, valine, and tryptophan. Restricting these has been shown to increase lifespan.

[@IrrasciblePoet]

Thank you Fixing the gut wall makes more sense. Reuteri perhaps? Trips in cleaves Arginine... Arginine is a pre cursor for Glutathione? Less inflammation? More of that coveted + NAd? Low Albumin : less oxygen, more tired, less strength, cold feet, . Checking for Addison's. What happens when you loose the pre fatty acid binding capability? Why is Albumin binding to bacteria derived metabolites important? Why is it important Albumin binds to Hurimic metabolites? I ask a lot, I have very low Albumin, exhausted all the time. Will thistle seeds help? Drinking lemon water? Thanks

[@conqueragingordietrying123]

Ah, what minimizes gut-leak in the large intestine may not in the small... If albumin can't bind to indoxyl and p-cresol sulfates (as examples), those metabolites directly damage the kidney and heart I'm not sure what can increase your albumin, but I'd recommend tracking intake with regular blood testing...

[@gmw3083]

​@@conqueragingordietrying123 Eating more eggs wouldn't increase albumin?

[@monnoo8221]

Albunmin is controlled and created by the liver... so, how does your liver look like? leaky gut can affect the liver, but such a lot of things can. What about your energy metabolism, your vitamin status?

[@GaiasFleas]

How do we get the digestive enzymes out of the organs once theyre there? I assume that's the next study we can try on humans, and see if epigenetic age changes.

[@monnoo8221]

agree. Lactoferrin as from chees, milk, colostrum, whey concentrate, is a natural inhibitor of tryptase and alerady being used for alleviating overshooting immune sponses, which rlaese trypsin as well. Unfortunately, tryptase has a functional role in the immune system. it is released by mast cells, eg in the context of allergic reactions. You may use this prompt in Gemini to see more details: "you say "The body produces natural inhibitors of proteases, including tryptase. These inhibitors can bind to and inactivate tryptase, preventing its excessive activity." which are they, how get they triggered, where do they get produced?"

[@juliahello6673]

Yeah, there has to be some kind of clearance mechanism

[@bhut1571]

Most interesting. Thankyou. I wish I wasn't distracted by the thin film interference in the right lens of the doctors glasses.

[@conqueragingordietrying123]

Ha, me, too!

[@plants_and_wellness1574]

I hope you ask him what a day of eating looks like and if not, why not 😩 I’m always so curious what these scientist eat.

[@conqueragingordietrying123]

Unfortunately, many scientists don't practice what they preach...Instead, it's good to see the published data, and then we can decide for ourselves, in contrast.

[@plants_and_wellness1574]

@ that’s a bummer. I know a lot of them follow a mostly plant based diet and eat fish a few times a week. I know I’ve heard Matt Kaeberline talk about how he used to not practice what he preaches but he does do better now and while I don’t know what all he eats in a day, he has mentioned having a massive salad for lunch most days. What are your thoughts on Morgan Levine and would you ever want to interview her?

[@paulfiedler9128]

@@conqueragingordietrying123 That's a good point. I email back and forth with another longevity KZbinr, and I don't think he eats very well-not like you or me, for that matter. Food quality is as important or maybe more important than the type of food. Eating CAFO beef instead of grass-fed beef is huge, for example. You are what your food eats. It's better not to be GMO corn.

[@conqueragingordietrying123]

@@plants_and_wellness1574 I'm a big fan of Morgan, I could definitely interview her on the channel-videos using her biological age clock, PhenoAge, are on the channel 7-8x/year...

[@sionnach.1374]

I mainly eat meat and animal fats. I feel great and look great for my age Normally 2 meals a day 1 24h fast a week 1 two fast bi-monthly

[@conqueragingordietrying123]

This isn't an anti-meat video, far from it. Pancreatic enzymes are higher during aging, and are involved in pro-aging mechanisms-what can we do in terms of diet, supplements, etc to minimize that?

[@websmink]

Very important and good work. Thank you

[@conqueragingordietrying123]

Thanks @websmink!

[@leonniceday6807]

So the research points to meals too rich in fat are bad? Any difference the kind of fat makes?

[@conqueragingordietrying123]

It might be a calorie intake story, as they used a 1100-calorie meal. Also, digestive enzyme leak is likely a transient process that stops after eating-what's the optimal fasting window after eating to allow for intestinal repair?

[@leonniceday6807]

@@conqueragingordietrying123 Thanks. For me at least it's a reminder not to eat too late in the evening. I suspect the species of gut bacteria also have a say in all this.

[@davidford8539]

Mike, do you measure pancreatic enzymes in your blood? If so which ones? Do you do time restriction on your feeding? Love this podcast!

[@conqueragingordietrying123]

Thanks @davidford8539! Not yet, but I'm looking into it. If I do, they'll have to be included at every test, so that I can track year-to-year change...

[@monnoo8221]

@@conqueragingordietrying123 your tryptase readings will mainly reflect your allergy, I am afraid... The positive side of seasonal allergies, at least I hope so, could be thatt the tryptase controlling systems are well trained, such as heparin, or lactoferrin.

[@henrywang4010]

Would taking growth hormone peptides help repair and restore the barrier to prevent the leak?

[@conqueragingordietrying123]

Not sure, but measuring pancreatic enzymes in blood (trypsin, elastase, amylase, etc) before and after could be a way to find out... Also measuring Alpha-1 Antitrypsin levels, which should inhibit proteases in blood...

[@henrywang4010]

that would be a great study. Or study the peptide bpc-157 in oral form that’s supposed to repair the stomach lining.

[@paulfiedler6820]

So are there conclusions specific to high protein or high fat diets being the main culprits in auto digestion? Maybe I’m killing myself with my ketogenic diet. And I’m now ruing the fact that I drank an entire bottle of Pinot Noir last night. It seems like alcohol might aid in causing a destruction of our auto digestive barriers?

[@conqueragingordietrying123]

One way to test that would be plasma levels of pancreatic enzymes (trypsin, elastase, amylase). If they're relatively high, then the approach might need work...

[@paulfiedler6820]

So we should get our blood tested for pancreatic enzyme levels? And, how often? Great video, Mike.

[@conqueragingordietrying123]

Thanks @@paulfiedler6820. When considering that autodigestive enzymes were higher in old rats, tracking year-to-year change (many tests/year) may provide insight into slowing the process...

[@Pnk690]

😱😱😱 tamda düşündüğümüz gibi.😶herkes yaşlı(!) safra kesesinin ,taşlarının rolü?😢thankyou so much professeur.

[@NYGuy2000]

Michael, hypothetically, if one took pancreatic enzymes after a stool test showed very low lipase and very high fat content - one of the functional medicine tests that yields enormous long-term gains 😊. Should one then try to minimize exogenous enzymes due to the accelerated aging risk?

[@conqueragingordietrying123]

Hi @NYGuy2000, the key would be minimizing any age-related increases for pancreatic enzymes in blood...the only way to know that is to track.

[@sooooooooDark]

i skipped thru quite a bit - so sorry if i missed major points that invalidate what im saying but: isnt this autodigestion issue simply a downstream cause by having a leaky gut (messed up villi)? may sound too simplified but yea - thats what it sounded like to me at least 🤔

[@conqueragingordietrying123]

Fixing a leaky gut in the large intestine may be relatively easy (soluble fiber--SCFAs), but what about in the small intestine?

[@sooooooooDark]

@@conqueragingordietrying123 not saying it was easy, but there r a few studies out there suggesting things like l-glutamine, curcumin, zinc, certain probiotics and then avoiding like dairy and gluten or individual trigger foods (i think?) to lower zonulin markers my point was more along the lines of "what hes presenting is what happens if ur small intestines rnt up to their task anymore" (not sure if i was clear nor if i understood him right 😅, but thats my summary of his presentation (that he seemingly didnt imply nor stated straight up(?))) i mean if this thing he presented was unrelated to leaky gut "and its own thing" (as in the digestive enzymes messing up the organism) then supplementing digestive enzymes would be kinda detrimental, wouldnt it? but i dont really think thats the case (it may only be the case if leaky gut is already ongoing and then the enzymes spilling into the bloodstream and whatnot)

[@nopara73]

mindblow

[@InquilineKea]

Free amino acids like arginine are an indication of excess blood trypsins?

[@conqueragingordietrying123]

Trypsin cleaves at arginine residues, so Geert mentioned that, yes, but also that many other peptides can be formed...

[@rhyothemisprinceps1617]

So... is taking bromelain bad? It is supposed to be orally bioavailable,

[@conqueragingordietrying123]

Good question-would supplemental digestive enzymes end up in blood? I don't think anyone's studied it...

[@rhyothemisprinceps1617]

@@conqueragingordietrying123 It has - Castell, 1995 'Intestinal Absorption of Undegraded Bromelain in Humans' ; article is available on ResearchGate

[@stonebridge7710]

@@conqueragingordietrying123 I'd guess the enzyme supplement crowd would have studied such. On another note, I was a bit distracted in the early part of the vid and didn't catch what treatment was done in the excellent rodent experiments, but I had the impression it was to improve mucin. If that treatment were GRAS then I'd prolly do it, but am now more eager than ever to get back to every other day fasting. Maybe continue collagen and key nutriceuticals in clear fluids. I'll probably go even less on dietary fat now.

[@juliahello6673]

pubmed.ncbi.nlm.nih.gov/9252520/

[@quiyoki]

how is cheesiella doing?