AGE Products Impact Lifespan: Impact Of Hyperglycemia, Kidney Function, And The Microbiome
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- Опубликовано: 16 апр 2022
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Papers referenced in the video:
Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan
pubmed.ncbi.nlm.nih.gov/18599...
Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression
pubmed.ncbi.nlm.nih.gov/17525...
Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N 6-carboxymethyllysine
pubmed.ncbi.nlm.nih.gov/35241...
Plasma Carboxymethyl-Lysine, an Advanced Glycation End Product, and All-Cause and Cardiovascular Disease Mortality in Older Community-Dwelling Adults
pubmed.ncbi.nlm.nih.gov/19682...
Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community dwelling women
pubmed.ncbi.nlm.nih.gov/19448...
Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor KappaB in PBMCs
pubmed.ncbi.nlm.nih.gov/12606...
Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans
pubmed.ncbi.nlm.nih.gov/30823...
Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants
pubmed.ncbi.nlm.nih.gov/31720...
Serum Carboxymethyl-lysine, a Dominant Advanced Glycation End Product, is Associated with Chronic Kidney Disease: the Baltimore Longitudinal Study of Aging
pubmed.ncbi.nlm.nih.gov/19853... 
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Amazing video. So clear. Im not an educated scientist but I can understand almost everything that you explain. Thanks!!
Vitamin C, Phenols, Quercetin, Turmeric, Resveratrol, Exercise do the trick with AGE
Super good video - interesting and well-explained. Thanks!
Thanks Katya!
Besides soluble fiber, omega-3 and vitamin K, propolis seems promising too. Paper title:
Propolis modulates the gut microbiota and improves the intestinal mucosal barrier function in diabetic rats
I've been doing a lot of research into senolytics and protein production mechanisms. By fixing protein production quality control, you may not even need senolytics, as waste management and repair seem to be differentially regulated by protein quality control.
I'm not sure if the same applies to Advanced Glycation End Products. I'm guessing the body can break down some of them, but others will be a more persistent threat.
I bet levels of Albumin might play a role in the buildup of Carboxymethyl-Lysine. What little Albumin the elderly have in their body becoming over glycated; but this is just conjecture.
Can we derive any heuristics from this research when it comes to protein composition & preparation?
So drink green tea
I thought I knew about glycation but gut permeability took me by surprise. I spent quite some time to figure out if exogenous sources made an impact but I didn't make the additional link .. thanks!
Thanks for posting this. Your videos often provide great information which is imo, quite unique & not available elsewhere. (without digging through hundreds of papers)
I've read that both acarbose and SGLT2 inhibitors extend lifespan (in mice) via the interventions testing program. They theorize the reason is that both of these drugs work to limit peak postprandial glucose. I wonder if the underlying reason could be that they limit the creation of AGEs. I'm imagining when in homeostasis, the body has an ability to clear AGEs, but at these peaks of glucose it struggles.
To fix this untested theory, I have started to walk after eating. I have the Contour next glucose strip system to check blood sugar 1 hour after eating. So far I've definitely noticed a difference between eating & sitting vs eating & walking. But I've only just begun, so we'll see what I find.
Thanks Matthew! I'm more familiar with acarbose, and your hypothesis that it may limit AGE as a part of glucose reduction makes sense. In addition, gut microbiome SCFA production is increase in acarbose-treated mice. SCFAs improve gut barrier function, so it may be a win-win for acarbose on potentially limiting blood levels of CML.
@@conqueragingordietrying1797 Supposedly Xylitol is a both a glycation inhibitor and a substance that increases SCFAs
"In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro."*
*Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota. Microbiome. 2021 Mar
"Xylitol, the nonnutritive sweetener, was reported recently
(Deo et al., 2020) to reduce AGEs"**
**Potential protein antiglycation, antiproliferation, and in silico study on the antidiabetic enzymes of bioactive metabolites from Adonis microcarpa DC and their ADMET properties, Journal of Applied Pharmaceutical Science,
2022.
}
Great video! In your opinion what is the best intervention to improve gut barrier function?
Thanks Tyler. Probably soluble fiber, which is fermented by gut bacteria into SCFAs, which optimize gut barrier function.
Thanks prof. LUSTGARTEN for this well-structured and clearly explained video.
The putative anti aging effects of metformin could probably be partly related to the fact that it decreases the level of AGE, and maybe especially CML, by impacting the microbiome. The fact that metformin reduces the level of CML, which is elevated in association with reduced kidney function, explains why numerous studies show the nephroprotective effects of metformin. It seems that data on this subject is still sparse and has not yet be studied comprehensively.
Thanks Abdelilah BENAHMED. Is there published data showing that metformin reduces CML?
@@conqueragingordietrying1797 sorry Prof Lustgarten but my answer to your question has been deleted twice.
@@abdelilahbenahmed4350 Ah, that's strange, not by me! It's very rare (like 1/1000) that I would delete a comment.
@@conqueragingordietrying1797 To summarize, some studies show that metformin could decrease AGE , including CML
Thanks for that,@@abdelilahbenahmed4350 ! To get around RUclips deleting comments, some post the title of papers, rather than the link-could you post those papers, so that others can see the data?
Hi Michael, good video as always. so it seems CR is one of the undisputed anti aging tactics. I do CR & IF and have achieved good age improvements in my blood tests. However I wonder if NMN & CD38 inhibitors ae really helping, or is it the CR. So a similar test / comparison for NMN would be great. Regards John Hancock
Hi John, and thanks. Do you have blood test data? That can help assess if CR, IF, NMN, etc. is positively impacting your health.
Here are two human studies:
Dietary Advanced Glycation End-Products (AGEs) and Mortality After Breast Cancer in the Women's Health Initiative (WHI) (n=2023) 15.1 year follow-up HRT3vsT1: 1.37, 95% CI: 1.09-1.74
Is dietary intake of advanced glycation end products associated with mortality among adults with diabetes? (n=3884) NS for 3.8 year follow-up
Thanks Paul-I meant dietary AGE product-all-cause mortality studies in generally healthy populations.
Whats an age product? harmful compounds that are formed when protein or fat combine with sugar in the bloodstream.
It would be interesting to know whether supposed AGE inhibitors (benfotiamine, carnosine etc. . ) actually extend life.
This is what Life Extension reports:
"Carnosine extended the life span of the treated mice by 20% on average, compared to the mice not fed carnosine.* The mice given carnosine were about twice as likely to reach the "ripe old age" of 12 months as untreated mice.
Carnosine did not alter the 15 month maximum life span of the senescence-accelerated mouse strain, but it did significantly raise the number of mice surviving to old age."
Of course, Life Extension sells supplements and every supplement they report on is often described as a wonder drug.
Anti-Aging Effects of Carnosine Report, Life Extension, Jan 2003
*Yuneva MO, Bulygina ER, Gallant SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Med. 1999; 2(4):337-42.
Would beta-alanine, which is converted to carnosine in vivo, have a similar effect? I would think so, but there's no testing to be referenced.
@@uBastianX I used to take that. Always made my skin tingle, like taking Niacin.
Carnosine suppresses expression of HIF1a, which is linked to issues throughout the body when it's in a state of oxygen deprivation. Not sure if directly, or if it addresses the problems linked to its over expression.
HIF1a can either turn off or turn on the key processes of mammalian regeneration. In the short term, it helps with regeneration and cellular repair. In the long term, over expression; especially in age, is linked to cancer, and conditions like endometriosis.
HIF‑1α promotes NLRP3 inflammasome activation which is linked to suppressed blood supply in fat, which makes it harder to burn off, and the cytokine storm in older versions of COVID-19, before omicron.
HIF1α inversely regulates steroidogenesis, and plays a role in cytokine and leukocyte production.
AKA Carnosine could be good or bad based on your age or condition. Probably beneficial.
Oh my.
The results showed that exposure of esterase to sugar, sugar phosphate and a steroid led to protein fragmentation and cross-linking and enzyme inactivation. Carnosine inhibited the cross-linking and inactivation, but not the fragmentation. The concentrations of sugars, steroid and carnosine used were higher than would be achieved in vivo but we are trying to simulate changes that may take years in the human tissues during the slow development of late life disease.
Steroid prednisolone-21-hemisuccinate is the steroid they were talking about. I don't know why they were hiding the name in about a dozen studies I've been looking at.
It's weird, but studying this, I think Carnosine combined with molecular Chaperone, alpha-Crystallin, may eliminate age's caused by sugars and sugar phosphates by restoring esterase activity. This may also restore normal steroidal functioning in ageing.
Skq1 boosts Alpha Crystallin expression.
Remains to be seen, though. Just conjecture from reading a bunch of studies.
Interesting content, I'm missing however AGE food content: it's mostly present in animal and processed food. Which is an additional reason to adopt WFPB diet...
Thanks Erast. Some AGE-product in food data was covered in this video:
ruclips.net/video/8gKFWBTpXWE/видео.html
Would love it if you did a video with Professor Pankaj kapahi on this topic.
Thanks for the suggestion, that's definitely possible
Any more data regarding this subject please anyone?
Not yet on the channel, but if there are papers you want me to look at, please post them!
Have you done any analysis with insulin load in your diet? It is an easy calc and you have all the data.
I started measuring insulin at every test 2 tests ago, and I'll do that for every test going forward. Once I have at least 5 measurements, I'll put it into a video. 2.9 on my last test, 2.2 before that for fasting insulin.
@@conqueragingordietrying1797 I meant insulin load formula from diet : carbs-fibre plus 0.56xprotein. I wonder what associations with your blood markers show up.
@@sathmath8544 I'm not worried about that-more important (to me) is the effect on the big picture biomarkers. If chronic dietary insulin load is a problem, we'd expect to see it in alterations to the other blood biomarkers in my data.
@@conqueragingordietrying1797 I understand, but I would at least check it against daily resting HR and HRV.
Great content! Again, thanks for your efforts! I want to say that Dr. Stanfield reviewed a study a few months ago that suggested IF is not significant with regards to potential benefits gained via CF with optimal nutrition. Looks like there are no CF shortcuts as of yet.
Thanks theedevil08. Do you mean this study?
ruclips.net/video/xkMYJs4JmXE/видео.html
What's AGE ?
Advanced glycation end products
Hi Michael, do you plan to make any videos about parasites? It's an interesting topic
Hi Rob, that's not on my direct radar because bacteria, fungi, and virus are the most likely culprits to affect health during aging. That doesn't mean that parasites aren't an issue, but I see that as an acute problem, rather than chronic, whereas the microbes are a chronic problem for aging and disease.
@@conqueragingordietrying1797 Thank you sir, so you plan videos about bacteria, fungi, and maybe(mold?) There seems to be a direct link with dementia.
Would be nice to know your views about silver nanoparticles, or any more "radical" approuch. There still seems to be no formal ways of combating the growth of harmful bacteria with age. At least to the point of having the microflora of when we were young.
@@roblim1767 The channel has videos on bacteria, fungi, and viruses, and also, I wrote a book!
www.amazon.com/dp/B01G48A88A
@@roblim1767 I also have a video specific to the bacteria question:
ruclips.net/video/uraF-eD4xgY/видео.html
@@conqueragingordietrying1797 Ow, it seems the main key is soluble dietary fiber.
I didn't know about this specific book of yours (sorry), I'll definitely read it this month.
Thanks for the reply, your interaction with subscribers is a big differentiator.
how about other AGEs? CML is not the only AGE
Yes, that's true, a video for another day!
Humans have a mechanism for dealing with AGEs that mice lack.
Human data is presented starting at 3:28
Conclusions: Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer.
That's not in the video, nor were papers cited that included that data. I'm sure other studies have shown that, though.
Fewer acronyms next time please