Rejuvant?
Has anyone heard of this?
The speaker presented a talk indicating that users got substantial drop in DNA methylation age results - I seem to recall an average of 8 years after 6 months usage
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Here’s a summary of CEO’s talk. Claims are quite impressive
https://www.longevity.technology/rejuvant-shows-positive-early-results-in-humans/
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Paul Beauchemin I found this study. Now this is interesting AKG shows life extension because it inhibits Mtor and activates AMPK. So thats good news and bad news. Good news because it is acting like both metformin and rapamycin life extension pathways. However the bad news is that it doesn't seem to be working by rewinding the methylation clock.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629006/
I will keep looking but I really don't see much. If this stuff is so great, shouldnt people be talking more about it and touting it for its antiaging properties?
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This is strange and was in the FAQ on their website:
Can I take Rejuvant with multivitamins?
Based on our data, taking multivitamins or other supplements that have many ingredients might not have additive effects. Because of this, we recommend taking Rejuvant apart from other supplements and vitamins.
Do I really need to stop taking multivitamins?
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Lifespan IO talked about it yesterday. I'll wait for better studies.
https://www.lifespan.io/news/pilot-study-results-suggest-epigenetic-age-reversal/
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Questionable 13-Site DNAm Clock?
On fightingaging.org, Reason says the following:
"The important point to consider here is that the TrueMe Labs assay is not a relabeling of any of the more established epigenetic clocks, those with significant research associated with their behavior. It is is its own beast, an independently developed test. It uses only 13 DNA methylation sites, and so it is very possible that it is much more sensitive to some interventions than others, in comparison to, say, the original Horvath clock, depending on which mechanisms influence those sites. Thus one cannot take any of the established research into the better studied clocks and use it to inform expectations as to how the TrueMe Labs assay will behave. 8.5 years might sound like a large effect size, but it is impossible to say whether or not that is the case."
In other words, the Rejuvenant claim about producing a DNAm clock reset is very questionable, because they used a nonstandard clock, possibly tailored to show a maximum effect. It would be a real service to the anti-aging enterprise if someone or some group would demonstrate, either systematically with mice or anecdotally with humans, that Calcium Alpha-ketoglutarate intervention actually significantly lowers the methylation age indicated by the Horvath clock.
Also, I note that there is a load of misinformation about DNA methylation on the Rejuvenant site. It characterizes DNA methylation as age-accumulated "rust" that randomly builds up with age. As I understand it, the correct picture is that genes are silenced by methylation, mainly by methylating sites in the promoter regions of DNA coding for making mRNA leading to protein production. Even infants have many methylated regions silencing genes that are not needed. As aging progresses, epigenetic programming silences some genes and activates others, and the methylation pattern shifts. Horvath's clock specifically selects hundreds of methylation sites that are best (positively or negatively) correlated with aging from 450,000 sites on an analysis chip. I'm not impressed by the results of a 13-site analysis.
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JGC said:
the Rejuvenant claim about producing a DNAm clock reset is very questionable, because they used a nonstandard clock, possibly tailored to show a maximum effect. It would be a real service to the anti-aging enterprise if someone or some group would demonstrate, either systematically with mice or anecdotally with humans, that Calcium Alpha-ketoglutarate intervention actually significantly lowers the methylation age indicated by the Horvath clock.Yes: I pointed this out earlier in this topic. I doubt they intentionally "hacked" it to turn out favorably for their product: the problem is that it's sloppy and not validated, not that it's intentionally pushed in one direction or the other.
Also, I note that there is a load of misinformation about DNA methylation on the Rejuvenant site. It characterizes DNA methylation as age-accumulated "rust" that randomly builds up with age. As I understand it, the correct picture is that genes are silenced by methylation, mainly by methylating sites in the promoter regions of DNA coding for making mRNA leading to protein production. Even infants have many methylated regions silencing genes that are not needed. As aging progresses, epigenetic programming silences some genes and activates others, and the methylation pattern shifts. Horvath's clock specifically selects hundreds of methylation sites that are best (positively or negatively) correlated with aging from 450,000 sites on an analysis chip. I'm not impressed by the results of a 13-site analysis.
So they're actually kind of right about this, though they've oversimplified. When you're developing from a zygote to a newborn and go through development to become an adult, your cells undergo regulated methylation under a developmental program aimed to turn you eventually into a functioning adult with all your cells doing what they're supposed to do. What happens in aging is very different: not an unfolding preprogrammed process, but a series of events all somehow involving damage that changes the epigenome in dysfunctional ways. This is a mixture of a very small number of stochastic events that methylate or demethylate genes that should stay as they are (direct epigenetic "rust") and regulated changes in cells as they have to adapt to an environment that has been changed by stochastic aging damage (what we might call secondary or downstream epigenetic "rust response").
Also, everyone keeps talking about "the Horvath clock." It's important to understand that there are now dozens of epigenetic aging clocks, including at least six developed by or with the involvement of Horvath, each of which is more or lesss good at different things. His original clocks were good at predicting calendar age, but not very good at predicting risk of age-related disease and death (biological age); the newer Levine "DNAm PhenoAge" is better at that (and the underlying PhenoAge clock is even better), and the "DNAm GrimAge" is at least as good and maybe better, though it "cheats" a bit by building smoking status into the clock.
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New rejuvant user here. I think it's amazing (as far as my exercise performance goes :P ). I'm combining it with 6mg weekly rapamycin, 500mg x 2 metformin, 5mg rosuvastatin, 500mg x 2 vit c, daily celery juice, garlic powder/AGE, magnesium, fiber, vit D... No issues to report after 4-5 days of use... except having a lot of energy to exercise :) We'll see how my bloodwork will be affected over time.
Life extension studies are solid (mice, worms, flies). Mice life extension is there (maybe ~3-4% on avg). Health extension is very significant. Turns hair darker ("better fur" :))... also reported by a forum member. Reduces ischemia in humans. There's some evidence AKG is an anti-cancer compound (works agains several cancer lines in cell and mice studies); reduces hypoxia. Human studies are limited, but that's ok as this compound has been on the market for decades and it hasn't harmed anyone. Safe to test N=1, imho.
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Guys, Rejuvant is extended (slow release), whereas other AKG formulations on the market are immediate release (as of 04/2021). I believe AKG is metabilized fast, and to get the same effect, one has to consume immediate-release AKG every 4 hours. I'm sure Rejuvant went through stringent quality checks as well, given the premium price and the brand they're building.
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Don’t know how true this is but I’ve read some “reliable” sources that AKG can reduce DNAm age. However, if you combine it with Metformin it won’t reduce DNAm age. Although there could be other beneficial effects. 🤷🏻♂️ I’m still undecided. I’m sure more papers will come out on this, hopefully sooner than later.
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I bought 180 500 mg AKG capsules for $15 on Amazon. Rejuvant's $110 monthly subscription price seems steep to me. I know my AKG from Amazon is not time release but in testing did the worms and mice get time release AKG? I think not.
The Rejuvant people say that they have a patent but on exactly what? For better or for worse, I expect to see copy-cat type extended release AKG hitting the market.
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AKG researcher, Dr. Gordon Lithgow was recently interviewed by Modern Healthspan. He doesn't seem to think that the CA from of AKG is superior. Another AKG researcher, Dr. Brian Kennedy was recently interviewed by the Skeekey Science Show. He stated that he saw no advantage of the CA form of AKG.
Kennedy has said that maybe the time release form is superior but tests are still being run to determine that.
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I'm on my last 5miligrams of rapamycin and have just become aware of AKG. Anyone know if they can be taken together? Just out of caution I thought I'd wait until my 1.25 month rapamycin cycle is through before tanking AKG. Also, my wife had a horrible case of ocular shingles after supplementing with arginine. She worries that AKG might set it off again but it seems that would be AAKG not AKG? Comments.
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Fred Cloud said:
Its the ca-akg that creates the sustained release,This is incorrect. Ca-AKG is just an AKG salt; it has negligible effects on pharmacokinetics. Rejuvant was formulated for extended-release characteristics.
Fred Cloud said:
AKG has been found to work also, so I think they just want something unique that they can patent so they can mark the price way up,This is fairly obviously not correct: I'm sure they "want something unique that they can patent so they can mark the price way up," but there's nothing unique about Ca-AKG, and it's certainly not patentable: lots of other people sell it at much lower prices. Rejuvant is more expensive in small part because of the additional cost of formulating an extended-release tablet, but also because the formula includes the additional ingredients (which are researched and patented based on mouse lifespan and frailty studies), the branding, the scientific affiliations, and the fact that it's being used in clinical trials.