CaAKG - the healthspan extender you need to know about?
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- เผยแพร่เมื่อ 12 มิ.ย. 2024
- Alpha-ketoglutarate (AKG) is a small compound, but plays a big role in our cells. Notably, AKG is a key component in the metabolic pathway, the Krebs Cycle. However, levels of AKG have been shown to decline with age. Delivered as a calcium salt (CaAKG), this recent publication (ref below) shows that AKG can extend healthspan in both male and female mice, and extends lifespan in middle-aged female mice. In this video, I will discuss in more detail what AKG is, the results of this paper and my thoughts.
TIMESTAMPS;
00:00 - Intro
00:56 - What is AKG? Aging connection
04:27 - Study results
08:35 - How/Why AKG has this effect?
10:00 - AKG in humans?
11:00 - Thoughts/Outlook
**reference at 3:42 should be doi.org/10.1111/acel.13059 Aging Cell. 2020;19:e13059 !!
REFERENCES;
Paper -- Asadi Shahmirzadi et al., 2020, Cell Metabolism 32, 447-456
September 1, 2020 ª 2020 Published by Elsevier Inc.
doi.org/10.1016/j.cmet.2020.0...
Press Release - www.lifespan.io/news/pilot-st... & pdlhealth.com/in-the-news/
Dr Kennedy Lab; www.buckinstitute.org/lab/ken...
Extends lifespan in C.elegans; Chin, R., Fu, X., Pai, M. et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 510, 397-401 (2014). doi.org/10.1038/nature13264
Pigs; Oncotarget. 2017; 8:91965-91978. doi.org/10.18632/oncotarget.2...
Gut Microbiome - The effects of dietary supplementation with α-ketoglutarate on the intestinal microbiota, metabolic profiles, and ammonia levels in growing pigs
doi.org/10.1016/j.anifeedsci....
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Icons in intro; "www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com - วิทยาศาสตร์และเทคโนโลยี
What a gem of a channel: anti-aging is probably my favorite obsession.
All of my family/friends completely dismiss my obsession and advise. For me, it's a lonely obsession.
Thanks Eleanor! This video is so well made! nice and simple! By the way I am the first author of the paper!
Thanks Azar - was a great paper! 😊
Thanks!
Thanks all for the positive comments! Just wanted to say the reference at 3:42, as was kindly pointed out, should be doi.org/10.1111/acel.13059 Aging Cell. 2020;19:e13059 !! (I did still use the other reference for research if you wanted to read more!) :)
Has it been research-proven that these AKG benefits can only be achieved with CaAKG, and not AAKG? Both deliver AKG to the cells, surely? And AAKG is cheap and readily available.
first of all I would like to congratulate you on being a very beautiful and smart woman... Now coming back to the CaAKG, Ive been researching for some sort of clarification with regards to a contradictory interpretation, I have towards CaAKG which brings benefits such as promoting skeletal and tissue muscle hypertrophy via mTOR signalling pathway. However, it seems that it may influence in promoting Senescent cell development, through the mTor pathway which demands more energy and growth in the body, and throwing cells into a frenzy state, increasing the rate on metabolic waste building up, thus the body has not time to clean it up at the required pace. Also an overacting mTor response is associated with cancer, diabetes obesity and certain brain diseases. And apparently blocking this pathway it actually helps the body to remove waste....So by definition CaAkG sounds more like a sort of anti-senolytic which does the opposite of senolytic, which greatly reduces the demand of NAD usage on waste clean ups of zombie cells?? Please don't get me wrong CaAKG on a short and brief period can be quite beneficial for those interested in building skeletal and tissue muscle's
@sheeky I appreciate you making this video. I know you cover other science subjects and hope you aren't tired of Aging videos. As a member of the HealthSpan movement I appreciate it!
Yes, these are excellent and very helpful to know. Thank you very very much! I have subscribed.
Excellent presentation! I find your videos to be easy to follow and, also, very informative. You succeed in making complicated subjects understandable. A great teacher!
That’s a huge difference with the mice models, so something seriously is happening internally. I would take the CAAKG and take a break on the weekends.
Thanks for another high-quality video! This AKG research is really interesting and I look forward to the results of the double-blind placebo trials. But, this is certainly something to watch for the near term. :)
Great concise overview of study and the ways AKG operates. New to the channel but will check out some of your other videos. You need more subs! Can't wait for the human studies. Thanks for making this video.
Thank you! 😊
PS: Thank you also for paper references and time stamps. Makes a huge difference.
As a follow on I wonder how exercise, time restricted eating, and other natural interventions modulate endogenous AKG. Reminds me of the NAD+ issue where the objective in older people is to help shift the NAD+/NADH ratio back to higher values. In the case of NAD it can be done by supplementing with NR or NMN or by fasting, exercise, or shrinking the eating window, or all of the above. We just don't know how much each of these helps and whether people doing time restricted eating, eating well, and exercising gain anything by supplementing. Same question for AKG. Looking at several papers it appears that increasing ketone levels might increase AKG, which if true might be a reason to eat in a way that elevates ketones for at least part of the day.
Sometimes some people need a push to get them to exercise. I also believe that these supplements are not only helpful in pushing people to do their exercise and keep active lifestyle, but also perhaps increase their confidence and motivates them to see results after 6 months or 1 year. The best part is that these are not drugs, but supplements. So, they are like most essential stuff in our cells.
Wow, really great video explaining the study. Thanks for making it!
The CEO of Ponce De Leon (that sells CA-AKG) said that he expects a much larger benefit to a time release version and CA AKG releases much slower than Arginine AKG. I would love a second opinion from someone not selling CA-AKG...
Thanks for your efforts to this comprehensive. I did learn something.
What a well-done this tutorial!!!
Thank you! 😊
Thanks for making the video. It is very well done.
Thank you, I am glad you liked it!
My new go to anti-aging videos! Gold nuggets of information and scientific papers explained in laymen format! Well done! Btw, are you using Doodley to create your videos? 👍👏
Thank you! 😊
Amazing video. Thank you.
Excellent content thank you for your time.
Excellent! Thank you.
Thanks for your all the wonderful video. Can you please tell me what the difference between Calcium alpha cataglutarate and Arginine AKG. I am always using Arginine AKG for No boosting effects before exercise.
This was very good . I hope this works for me.
this is really exciting news~~
Wow! Your analyses are amazing. Thanks!
Another fantastic video, thanks Sheekey. Did they use the Calcium form for all their cohorts? Why use the Calcium form? Better bioavailability? DO they have a patent on the Calcium form or AKG?
Thanks! Yes, CaAKG was given to the mice, they don't state why that form, but possibly better bio-availability and this is the declaration of interest which may help with the last q; G.J.L. and M.L. are co-founders of Gerostate Alpha, a company aimed at developing drugs for aging, and are shareholders in Ponce de Leon Health. D.E. and Azar Asadi Shahmirzadi are shareholders in Ponece de Leon Health. B.K.K. is a board member and equity holder at Ponce de Leon Health. G.J.L., B.K., M.L., D.E., and Azar Asadi Shahmirzadi are named inventors on a preliminary patent application related to this discovery.
@@TheSheekeyScienceShow Thanks for your reply. I ordered some today. It comes with a pre/post methylation test but I'm not so sure how good it is, no studies submitted on its accuracy AFAIK.
Thank you Dr. Sheekey.
I heard that AKG increases NO2 and that methylene blue surpresses NO2.
If one has both on hand, from a biochemical standpoint, do they antagonist each other?
Can one take both in a day and still get the benefit of each? Thank you.
Nice informative video thank you. What happens to the Calcium in the body? Does the body use it? Discard it? Is the calcium a supplement like the one they add in milk? Can we have too much calcium because of this supplement?
How do these things hold up to the digestive process and is there a preferred dosage?
Hmmmm. Thanks for this. Might add this to my repertoire (Resveratrol, ALA, Vitamin D3,...)
20g CaAKG for 17 EUR. www.hansensupplements.com
Thankssss!!
Awesome content
Hi Sheeky Scientist. Is AAKG a good choice for supplement? Or best without the added amino acid arginine? Can you recommend good source? Does it need the calcium?
I heard that that mouse trial had vitamin C deprived mice. So there is a chance that the Ca in CaAKG was what gave the mice a longer life.
I need to know what software you're using! I need this!
I think you should publish a book "Longevity and how to obtain it". Your knowledge is outstanding. Publish on Audio Books so I can listen as I go to sleep...great work.
Thanks! Am definitely considering but at least not until I finish my PhD!!
Actually, the same health improvement can be achieved for peanuts by taking more than 2 g of citric acid or any citrate per day. AKG can be produced in our body from citrates.
And indeed, if to use citric acid with meat, the advantage will be better protein digestion. Or with water - it also will help but in lesser extent.
Sounds like Apple Cider Vinegar?
@@oibal60 Nope. Citric acid is not vinegar acid. Citric acid works better.
Potassium citrate supplements can boost AKG levels in our body?
@@francisdza179 i consume a lot of potassium chloride (twice more than table salt) and some amounts of citric acid instead. And feel great. But may be from other supplements too. I keep my TH-cam channel on the subject, if you are interested. Cheers
@@Dr_Oleg_Kulikov Thank you.
Wicked Smaht !!!
Could one just incorporate a calcium tablet in addition to aakg and get the same effect?
Dear Ms. Eleanor - would you suggest supplementing with L-Arginine Alpha-Ketoglutarate, or with Calcium Alpha-Ketoglutarate? Do they act in a similar way?
I think the CAAKG is better
Is alpha-ketoglutarate the same as alpha-ketoglutaric acid? I am a bit confused, sometimes these names alternate in articles, but some sources say one is a derivative of the other.
For healthspan and lifespan we should take advantage of nanotechnology. Thus the following supplements should be taken in liposomal form: alpha-ketoglutarate (Ca-AKG), apigenin, berberine, curcumine, glutathione, magnesium, NAD+, NMN, NR, spermidine, trans-resveratrol, and vitamins B12, C, and D. 💕☮🌎🌌
Thanks.
What's the difference between regular AKG found in most AKG supplements and CaAKG as far as this is concerned? Do we need the Calcium form for the anti-aging benefits?
Likely differences are in bioavailability but given this study only gave the mice the CaAKG form it cannot be concluded if the other forms would have a similar impact
Was the double blind trial completed and released ?
Did they use the time released version in the animal studies?
It's interesting to supplement to increas things as AKG and NAD+ because they decrease so much with age.
But wouldn't it be even more interesting to know why they decrease?
With NAD+ I suspect things like CD38, a big consumer of NAD+.
But do we know what is it for AKG?
I've read that the anhydrous form of calcium AKG has better bioavailability. Can anyone confirm this?
Thank you. One issue with the mouse study is that they used CaAKG, and that compound will also deliver calcium to the bloodstream as I understand it. Do you have any thoughts on whether the potential AKG benefits to the mice can be distinguished from possible benefits from the Ca supplementation?
Shhhh, but i interviewed Brian Kennedy this week and asked this exact question.. Unlikely that its the calcium basically. Should have the video out next week
@@TheSheekeyScienceShow Great - look forward to that one
Thanks for that. BTW - to appear to be loking directly at the viewer you look at the top of the lens frame on the camera you are using. This prevents the illusion of a deep interest in low-flying UFOs.
I’m also interested to stop aging process in a human cell
Would you recommend taking the Calcium-AKG in capsule form as in the rejuvenate capsules or directly in powder form? Which do you think would be better?
I wouldn't know, sorry!
I have a question. AAKG take like CAAKG in case anti aging.
any updates on the double blind study?
Is calcium AKG water soluble?
Is there a version of this which would be safe for small parrots?
what about okg and aakg, are these a source o akg too?
I weigh 150 pounds. So 2% weight / weight means 3 pounds of AKG per day.
Do I understand that correct? That sounds completely nuts.
Is there a big difference between the effect of Ca-AKG and AAKG?
Good question, wondering the same.
I think the differences might be pharmacokinetics - LifeAKG is supposed to be more of an 'extended release' - though I'm not sure if that is dependent on it being the calcium salt or other aspects of how it is formulated. Sheekey says it may be more bioavailable.Use of Ca AKG in the studies may have to do with the proprietary supplement formulation (Brian Kennedy is involved with the company that sells Ca AKG as 'LifeAKG').
My thought was that they may have used the Ca form to avoid the possibility of Arginine confounding the results given that arginine has physiological properties of its own. The other possibility is that AAKG is not patentable or someone else has the patent on the manufacturing process.
Which works best for women AAKG or Ca-AKG? I read that AAKG works better for women & Ca-AKG for men. Wrong???
From my understanding those inflammatory markers are secreted by senescent cells to signal our body to get rid of it. Wouldn't the suppression of this secretion caused by AKG supplementation cause a net accumulation of senescent cells theoretically?
First sentence = true. However, what appears to be the case in aging is that maybe the inflammatory phenotype weakens so is less effective at recruiting and so remains and you end up with chronic inflammation which can further cause disease. Moreover, immune cell function declines during aging so even with the inflammatiory factors removal of senescence cells decreases with age and hence senescent cells accumulate! I can see why it can be confusing...it's even harder to study :D
Very interesting! Would it be worth it to thake the bodybuilder supplement?
Thanks and unfortunately that is not a decision i can make for you, hope you understand 😊
@@TheSheekeyScienceShow unsatisfactory. the gains must be made.
would any one happen to know where one could acquire some of this substance and what doseges it should be taken at
There are some comments on this reddit thread, may help :) www.reddit.com/r/longevity/comments/ikpyxa/caakg_the_healthspan_extender_you_need_to_know/
Amazon.com
20g CaAKG for 17 EUR. In April is15% off. www.hansensupplements.com
Question, But Doesn’t Glutamine FEEDS Cancer?
I would love to hear a conversation between you and Dr Brad Stanfield just about longevity in general and supplementation to increase it
Perhaps you could include Rhonda Patrick in that
i cant buy it anywhere D:
I am Personally interested in the effects CaAKG would have if you gave it to dogs. Dogs grow up so fast and because of how fast they grow up they don't live as long(bigger the dog the shorter the lifespan). so if per say it slows down the initial growth that is so detrimental to dogs life span would the life span be extended just by giving it to then while developing.
Just love cutting edge anti-aging products that may extend life and healthy to the end. I want to live 200 years like a tortoise lol. I would cycle any cutting edge anti-aging products like one week on, one week off. Everything being new and experimental I would cycle To purge my system of any overt negative build up of waste and toxins. Drink lots of water.
How does AKG differ to AAKG? does the body tranform AAKG into AKG ?
AAKG, is arginine-AKG and so is the amino acid arginine bound to AKG.
@@TheSheekeyScienceShow Thanks! Do you have any idea if this is then different to supplementing with straight AKG or will the body metabolise it so it's sorta equivalent?
@@grasshopper33xx Honestly, no, but there would definitely be a difference as for every molecule of AKG there would be an arginine. Arginine has other effects on the body such as altering nitric oxide levels
@@TheSheekeyScienceShow Perfect thanks, I'll keep an eye out for the coming research, looks super interesting
first of all I would like to congratulate you on being a very beautiful and smart woman... Now coming back to the CaAKG, Ive been researching for some sort of clarification with regards to a contradictory interpretation, I have towards CaAKG which brings benefits such as promoting skeletal and tissue muscle hypertrophy via mTOR signalling pathway. However, it seems that it may influence in promoting Senescent cell development, through the mTor pathway which demands more energy and growth in the body, and throwing cells into a frenzy state, increasing the rate on metabolic waste building up, thus the body has not time to clean it up at the required pace induced by CaAKG. Also an overacting mTor response is associated with cancer, diabetes obesity and certain brain diseases. And apparently blocking this pathway it actually helps the body to remove waste....So by definition CaAkG sounds more like a sort of anti-senolytic which does the opposite of senolytic, which greatly reduces the demand of NAD usage for clean up of zombie cells... Please don't get me wrong CaAKG on a short and brief period can be quite beneficial for those interested in building skeletal density and muscle volume.
i agree, it's complicated and doesnt really make much sense. Why? CaAKG is likely having a plethora of effects with modulation of mTOR being just one of them. I don't think we can truly say what aspect of akg was causing the effects seen in this study yet, neither do we know how akg and other compounds like rapamycin would work in tandem....science!
@The Sheekey Science Show wow thank you for responding(you made my day)... I am a sort of a natural bodybuilder who's on the lookout for ways to optimise the body on a cellular level, unlike the typical bodybuilder who focuses primarily on boosting hormones ...I read quite a lot about CaAKG and consumed it for 2 years and my experience on taking it everyday was great(optimising muscle strength, hair & nail growth).However by the the 3rd month I was beginning to feel some side effects particularly on the left hemisphere of my brain(the hypothalamus region to be more precise). side affects such as fogginess and minor cognitive impairment... Anyways felt that I had the moral obligation to share my personal experience with Caakg......... Love your videos, however with such a beautiful face I believe that you should do more interview vids, it stimulates further emotional attachment from your followers through the visual pathway
Is this compound similar to Alpha Lipoic Acid in any meaningful way?
No where close
hey sheekey, have you decided what you want to do in life, I mean, what you will specialize him?
Hmm, no, not yet, am already specialising in senescence /p53 anyway from PhD, but would always want to learn different scoence disciplines for a broader perspective!
Good luck, Sheekey - you have a gift for explaining complex things. You will do well wherever you end up. Thanks for teaching us along the way.
also would you be interested in talking about Ashwagandha i don't take it. but i just started seeing on my youtube feed
currently know nothing about it, but will consider as a future topic :)
@@TheSheekeyScienceShow thanks :)
will AAKG have do the same as Ca-AKG?
We are all wondering the same exact thing. No one seems to be able to give a clear answer, except that Ca-AKG probably has more bioavailability and that’s probably why it’s more expensive too. ;)
Yea I was wondering that. .AAKG molecular structure: C6H14N4O2 (L-Arginine) C5H6O5 (Alpha-Ketoglutarate), Ca-AKG molecular Structure: C5 H6 Ca O6. . soooo. . I dunno.. I think so. my guess.. I think AAKG is actually two ingredients, l-arginine and Alpha-Ketoglutarate
Sooooo.. yeaaa I should get some?
Is there a kerbs cycle in worms ?
*Krebs, yep
Imagine if they started feeding the mice before they were 60 (in human years)
Can AAKG have same effect?
Not assessed in this study so not known. Arginine is likely to have a difference, in particular as it is an amino acid
@@TheSheekeyScienceShow I've tried to find how arginine alpha ketoglutarate is metabolized to see if arginine and alpha ketoglutarate become bioavailable in the serum or if they enter a pathway that ties them up, but I cannot find anything on AAKG metabolism.
akg is cheap and has been used by ALS patients following deanna protocol, which they have to take akg on every waking hour.
They use arginine AKG; the arginine may provide additional benefit as arginine may inhibit formation of protein aggregates: medicalxpress.com/news/2020-05-arginine-potential-disease-modifying-drug-polyglutamine.html
Arginine is better known for increasing NO production, which I have questions about as increasing NO without adequate peroxynitrite scavenging could be harmful. Also, arginine ups mTOR which suppresses autophagy - which could be either good or bad in neurodegeneration. In general I would say more autophagy is good (esp. mitophagy), but there may be cases even when considering the same illness (e.g., Parkinson's) of individuals with problems with excessive autophagy causing accelerated neuronal loss.
I love this kind of research, not only the way they want to extend or lifespan but doing it so we can be healthy too. I don't really want to live like 150 years but 50 of them will be me in a bed or sick xd
How many years of research do you think this will be avaliable for everyone if proven successful? Like 10 years? Maybe 15?
Too early to say at the moment!
:(
Well, its currently available and fairly widely used among bodybuilders.
True, just more rigorous clinical trial looking at aging biomarkers would be needed to be convincing! 😊
@@TheSheekeyScienceShow True! I won't start taking it anytime soon. Apparently, David Sinclair has put it into his daily regimen, which is interesting.
Well she does have a pretty speaking voice so she's got to be intelligent 😁😁 and not one of you people take the supplement I bet🤔🤔🤔 I have taken it several times now I got some good results and I've had some strange side effects.
hey Eleanor, I wonder: every time some lab discover something new, you guys that are already in the field are something like in the VIP area, what means you people in this biomedical field are always 100 steps forward compared to us mere mortals, that live in the dark.
But how much of newspapers in the aging field really affect how you live? I think I saw somewhere that you already take some supplements related to aging healthier, but I don't remember where. I know it's very personal but does be in the field really gives you an advantage compared to people in other areas, or new discoveries don't affect your life at all, maybe because you don't care? Do you see any difference in healthy and aging compared to people around you? Not being rude, its pure curiosity. And that is not the time to be modest, .
I think it would definitely depend on the individual. As scientists we tend to be more concerned about the data and reproducibility and the underlying biochemical mechanisms woth any claims. But with regards to the first point, we may get to know about such claims from research presentations before it becomes public but again we are overwhelmed with so much information i dont think it would make much difference! 😊
Thanks for the very informative video! Definitely going to follow up on this. By the way, your hair looks like a string of nucleosomes.
Dna!! (minus histones)
Wouldnt calcium cause kodney stones.? I dont think this supplement might be wiese.to take until theu clarify it and do himan tests.What do yoi think.Are you a graduate ?
Shut up and tell me where to buy this CaAKG!
Amazon.com
Aononymous...LMAO
20g CaAKG for 17 EUR. In April is15% off. www.hansensupplements.com
PogChamp
Rejuvant CaAKG is difficult to implement
1) cant take with other supplements
2) must be taking on empty stomach in morning
3) must not take other supplements until the evening
this destroys my supplement stacking schedule.
for example, if I use berberine to address glucose at meals, using CaAKG, means I can not take berberine to address glucose.
Im canceling my subscription to this expensive and horribly awkward dosing schedule.
So, you mean we can't also take Vitamin, mineral, etc. as well? I take:
Tru Niagen NR in the morning, an hour after coffee,
Zinc + Copper, Vitamin D3 + K2 & Magnesium, Super B-Complex, TMG and also planning to include Sirt6 Activator.
From my understanding, TMG also relates to DNA methylation as AKG. So, should I remove TMG.
Please let me know what all of the above I can take with CaAKG.
Thank you!
Please continue to say 'autophagy' correctly - ignorance needs to be pushed back.
Too many...
Thanks but for me your voice is irritating...lol
A