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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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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Peter H. Howe You go boy! 🥳🎈🙏
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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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Larry Also reddit comments: https://www.reddit.com/r/longevity/comments/hj6zvv/results_of_nonplacebocontrolled_study_run/
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Paul Beauchemin
Thank you for the links. The you tube interview was great. I think they don't recommend taking AKG with multivitamins since the combination might cancel out each other's positive effects. At least that is how I interpreted what he said. They have seen that happen when they have tried to combine other products. Products that on their own had positive effects but when taken together the positive effects of both products vanished.
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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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Iðunn
About your "stocastic events": there is likely some random methylation that happens to DNA in particular cells, but that should be extremely unlikely to effect all DNA, so that it would show up in an overall methylation assay for a clock estimate. Or perhaps you had in mind random epigenetic reprogramming events from some feedback mechanism that went astray. I don't know of any information about that.
I also note that the Rejuvenant site also says: "Methyl groups are chemical tags, that in effect block our DNA from doing its job when it comes to making ideal copies of itself ..." That's wrong. In cell division the methylation pattern is copied along with the rest of the DNA structure. Otherwise epigenetic programming to determine cell function wouldn't work.
Finally, I wonder how TrueMe Labs picked their selected 16 methylation sites, if it wasn't done to optimize their age-reduction effect. As I said, if you use the right chip, there are hundreds of thousands of methylation sites to choose from.
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Iðunn
On the matter of bio-clocks, in his 2020 ARDD Meeting talk on Friday, David Sinclair presented evidence from his mouse-based experiments that when his OSK cocktail of Yamanaka factors is used to reset the DNA methylation clock of aged mice, it also resets the gene expression to a profile characteristic of young mice. In other words, resetting the DNAm clock (at least using OSK) also resets the biological age. I consider that to be very good news.
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JGC Did Sinclair mention if it caused any deformities?
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Jim N well sure you may grow an extra toe, but thats the price you have to pay to live past 100.
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Jim N
Next week you should be able to view the recording of his talk yourself on the ARDD site. From my understanding and memory, what his group did was this: (1) injure a mouse in a particular way; (2) show from DNAme testing that the methylation pattern had been modified in the injured tissue to map into that of an aged mouse; (3) apply a virus that implanted OSK-generating genes in the damaged tissue only; (4) demonstrate that the damaged tissue had recovered its function; (5) demonstrate that the DNAm methylation pattern of the tissue had been restored to its former youthful profile.
There were no deformities, but one would not expect any. Sinclair did say when introducing discussion of the experiment that if you simply dosed yourself with OSK, it would kill you. Here's his slide showing the DNAme comparison:
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JGC What is the dosage with OSK? What does O, S and K mean?
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Pablo Reinaldos López
OSK stands for three of the four "Yamanaka Factors", four proteins designated by the acronyms OCT4, SOX2, KLF4, and c-MYC (OSKM). There is no "dosage" involved. The researchers genetically modified a strain of mice using a virus that implanted a "cassette" in their DNA. This produced a setup in which, when a certain exotic antibiotic was present, the cassette would switch on the expression of OCT4, SOX2, and KLF4. (They omitted c-MYC because there was some evidence that it causes tumors.)
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I ordered some this week. I’ll tell you in four months if I see anything. I also take rapamycin weekly, do you thinks it’s a bad idea to combine the two?
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Larry Wonder how your experiment is going? Thanks!
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Larry who knows, it might have some great synergy.
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Larry I"ve been using Rejuvant and Rapamycin for the past 4 months... no issues. But would be really nice to see all the permutations and combinations of common age-mitigation drugs and supplements tested ... sample size n=1 is a lousy way to live our lives :-)
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Hi, I noticed many available akg supplements available in ~300mg caps- is this what an “effective “ daily amount should be to start?
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Al m Rejuvant (and the studies done by the Buck Institute) are all Calcium AKG... not the other versions of AKG. The Rejuvant dosing is recommended 1 gram per day (2 tablets), but I've done 1 gram in morning, 1 in evening for the past 3 months. I have also tested the powder from Maxx herbals... definitely looking for less expensive options: https://www.amazon.com/Maxx-Herb-Calcium-Alpha-Ketoglutarate/dp/B08BW7D4TZ/ref=sr_1_2?dchild=1&keywords=Calcium+akg&qid=1613084575&sr=8-2
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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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I have taken 2 different DNAm tests and after 6 months of Rejuvant it did not lower my epigenetic age in either test. I'm debating on whether to continue taking Rejuvant...
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Jimmy2 Well thats a bummer. Did you use their recommended lab trueme or a different dna age test?
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