201 replies to this topic

[Michael]

FYI If you want to reference a post you can link to it directly.

 

What was used in the study (and in every other such study that I've seen so far) was this

 

α-Ketoglutaric acid

https://www.sigmaald...S&focus=product

 

That's what I was referring to, apologies for any confusion.

You're either misremembering, or misstating your understanding, or have read a highly unusual subset of papers (including not reading the abstract of the paper that set off this thread). The vast majority of studies in mammals (including humans) as opposed to in vitro studies and studies in invertebrates have used AKG salts — usually Ca-AKG — not the acid, which as noted in the post you and Harjkin are referencing can only exist in solution (whereas salts can be mixed up in food, as in most animal studies, or put in pills or powder, as with the human trials); in this new bone study, they delivered it by putting it into the animals' drinking water.

[Nate-2004]

Seems like most the options available are AAKG for some reason. I came here to ask why this is the only thing available out there and why arginine is so commonly combined with AKG. Would this even matter? I’ve been putting AAKG in my smoothies the last month. I’m actually not even sure of what the dosage should be so I’ve used a Tbsp each time, or what seems to be about 1400mg AKG and a whole lot more arginine.

[TMNMK]

Seems like most the options available are AAKG for some reason. I came here to ask why this is the only thing available out there and why arginine is so commonly combined with AKG. Would this even matter? I’ve been putting AAKG in my smoothies the last month. I’m actually not even sure of what the dosage should be so I’ve used a Tbsp each time, or what seems to be about 1400mg AKG and a whole lot more arginine.

 

No idea why Arginine specifically in those cases, I don't take that form. But search for "ketoglutaric acid" and some things should pop up, it's readily available as calcium and magnesium salts.

 

EDIT: and not terribly expensive, I do not use that one expensive brand with all of that marketing behind it, seems silly to me when it is available for a much lower price. As far as dose, I do maybe 3.6-4.8g/day so far no problems - clearly not dead yet.

Edited by TMNMK, 05 December 2020 - 03:46 PM.

[aribadabar]

 it's readily available as calcium and magnesium salts.

 

Would you share a source for Ca/Mg salts?

[Krell]

Today I subscribed to the Rejuvant package that includes daily CaAKG and a DNAging test.  I will post when I get some results

 

Age 75

 

After taking CaAKG for 3 weeks, I finally got around to sending in my TruAge saliva biological age test.

 

Got the results today and it shows my biological age as 51.1 versus my chronological age of 76.1.

 

Looks like I did a good job picking my ancestors!

 

Either that or 3 weeks of CaAKG works wonders.
 

Here is an interview with the TruAge creator

https://biohackstack...s/truage-index/

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[Harkijn]

After taking CaAKG for 3 weeks, I finally got around to sending in my TruAge saliva biological age test.

 

Got the results today and it shows my biological age as 51.1 versus my chronological age of 76.1.

 

Looks like I did a good job picking my ancestors!

 

Either that or 3 weeks of CaAKG works wonders.
 

Here is an interview with the TruAge creator

https://biohackstack...s/truage-index/

The problem is you told them your chronological age. An interesting way for you   to get to know reliable data, would be to let someone else send in your saliva.

[Starchild]

After taking CaAKG for 3 weeks, I finally got around to sending in my TruAge saliva biological age test.

 

Got the results today and it shows my biological age as 51.1 versus my chronological age of 76.1.

 

Looks like I did a good job picking my ancestors!

 

Either that or 3 weeks of CaAKG works wonders.
 

Here is an interview with the TruAge creator

https://biohackstack...s/truage-index/

 

Do you know before and after? Or, will you get another reading say in a couple of months? Just trying to understand the effect of CaAKG. 

[VP.]

I sent mine in before I started CaAKG. It took 6 weeks for a result of 55.5 when my chronological age is 59.9. 

[Krell]

Do you know before and after? Or, will you get another reading say in a couple of months? Just trying to understand the effect of CaAKG. 

No, sorry I have only one TruAge test result taken after 3 months of taking CaAKG daily.  My bad.

 

But I do have a previous biologic age test from April 2018 by Osiris Green where they measured 59.5 yrs when I was 73.5 yrs old. Both tests required me to give my true age.

 

https://www.longecit...e-3#entry845679

[Onur]

There is no ca-akg in my country. There is arginine-akg, does this show the same effects?

[aribadabar]

There is no ca-akg in my country. There is arginine-akg, does this show the same effects?

 

Yes, if you take 3x the amount.
 

[Onur]

Yes, if you take 3x the amount.
 

How much is this amount? Is 5000 mg enough?

[Oakman]

There is no ca-akg in my country. There is arginine-akg, does this show the same effects?

 

I asked the study's author. The answer was somewhat ambiguous.

 

https://www.longecit...ndpost&p=898406

[aribadabar]

How much is this amount? Is 5000 mg enough?

Some AAKG is complexed 1:1, other 2:1. But even at 2:1 , 3-5g is sufficient, yes.

[Krell]

I asked the study's author. The answer was somewhat ambiguous.

 

https://www.longecit...ndpost&p=898406

 

Here is the label on the Rejuvant "LifeTabs" that shows their recommended dose of Ca-Akg (2gm/day)
 

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[aribadabar]

Here is the label on the Rejuvant "LifeTabs" that shows their recommended dose of Ca-Akg (2gm/day)
 

 

The label says 2 tabs= 1000mg ( i.e.500mg/ tab). The serving size is 2, not 1. Therefore, the recommended daily dose is 1g.

Edited by aribadabar, 20 December 2020 - 09:02 PM.

[Krell]

The label says 2 tabs= 1000mg ( i.e.500mg/ tab). The serving size is 2, not 1. Therefore, the recommended daily dose is 1g.

 

Yes you are right.  And I just weighed 2 tablets together and they were ~1.5 grams on my 0.1gm  kitchen scale. 
 

[QuestforLife]

I finally got the results back for my Sept TruMe test.

Chronological Age: 41.8
Biological Age: 36.7

There has been an improvement at the 6 month point. It is not clear whether this is simply because I just took AKG for longer, or because of anything else I added at the 3 1/2 month point. Be warned TruMe have now become very slow making further testing difficult. I discontinued AKG after submitting the Sept test due to fatigue. I may restart it in the future at a lower dose or perhaps intermittently.

Kirkman Labs worked fine for me - 900mg/day (3 tabs) of the mixed magnesium+calcium salt of AKG. So there is no need to pay the extortionate amount Rejuvant charge.

Edited by QuestforLife, 21 December 2020 - 08:05 AM.

[HaplogroupW]

Here's another calcium AKG source.

https://www.simplesa...0-capsules.html

 

[QuestforLife]

I finally got the results back for my Sept TruMe test.

 

Chronological Age: 41.8

Biological Age:  36.7

 

There has been an improvement at the 6 month point. It is not clear whether this is simply because I just took AKG for longer, or because of anything else I added at the 3 1/2 month point. Be warned TruMe have now become very slow making further testing difficult. I discontinued AKG after submitting the Sept test due to fatigue. I may restart it in the future at a lower dose or perhaps intermittently.  

 

Latest TruAge results from Jan 2021

 

Chronological Age: 42.1

Biological Age 35.5

Delta 6.6 years

 

Biological age continued to fall from 36.7 to 35.5 years despite 4 months passing between tests.

 

How do I feel? Fine, nothing significant to report. The first traces of white in my beard continues to very slowly advance. The good news is that I have no fatigue this time and my weight lifting has not been affected like last time.

 

What was different? I stopped my enhanced saturated fat diet in October. I am guessing this was responsible for the fatigue. I had a break from AKG from the start of Sept to mid November 2020. Then I started off on only 600mg/day AKG (kirkman labs salt) rather than previous 900mg/day, but this time alongside 500mg berberine. I reasoned AMPK activation would increase isocitrate dehydrogenase , which should increase the production of AKG in the krebs cycle. Interestingly, berberine caused no weight loss, which it has in the past. I did increase my AKG dose to 900mg/day from mid-December (when the lower dose caused no fatigue).

[TMNMK]

Was this one posted previously? Just happened across it. https://onlinelibrar...1111/acel.13291

 

Not too much, not too little, just the right amount of aKG helps out apparently. 

[Guest]

Here is the label on the Rejuvant "LifeTabs" that shows their recommended dose of Ca-Akg (2gm/day)
 

 

I'm a little confused:

 

 

according to the label, one serving (2 tablets) of Rejuvant contains 100% of the RDA of preformed Vitamin A. Why?

 

 

To get the effect size that the mice study implicated, one would need to take 17 to 30 servings per day. This sound like an uncomfortable amount of preformed Vitamin A - toxicity is a real issue.

 

 

Is there is a source for affordable Ca-Akg without Vitamin A, so that everyone can take 17 gram every day? Otherwise there is no evidence that it is indeed life extending (certainly not with that amount of Vitamin A in Rejuvant)?

[Harkijn]

Was this one posted previously? Just happened across it. https://onlinelibrar...1111/acel.13291

 

Not too much, not too little, just the right amount of aKG helps out apparently. 

 

I am not sure if this  was posted before but it is again interesting to see that  AKG in drinking water has  a positive effect on mice.

I have been taking a tablespoon per day of AAKG since october. Per this thread  I should take small amounts spread over the day, but I have not got round to that.

A number of Rejuvant takers have not posted anymore, wonder why....

[TMNMK]

I am not sure if this  was posted before but it is again interesting to see that  AKG in drinking water has  a positive effect on mice.

I have been taking a tablespoon per day of AAKG since october. Per this thread  I should take small amounts spread over the day, but I have not got round to that.

A number of Rejuvant takers have not posted anymore, wonder why....

 

Yeah that's interesting, I don't know why they haven't. I'm not using that brand and haven't really looked closely at their label wrt Vitamin A more specifically. I do mix of Ca- Mg- salts available online. Yeah it is interesting and I like that they looked at a variety of concentrations across a spectrum of areas as it appears at least in their murine models to not be simply diminishing returns but actually a sweet spot whereupon higher concentrations lead to reversal of benefit.

[escape]

A number of Rejuvant takers have not posted anymore, wonder why....

 

Currently there is a very long delay getting results for the Trume DNA methylation tests (the free test that Rejuvant provides.)  It took mine just over 3 months to come back. This is just my control (day 0 of Rejuvant.) I'm due to get my next free Trume DNA test from Rejuvant in a couple months, but then maybe add another 3 (?) months to that for getting back the results. I'll post my results when I get them. 

[Michael]

All:
 

After taking CaAKG for 3 weeks, I finally got around to sending in my TruAge saliva biological age test.
 
Got the results today and it shows my biological age as 51.1 versus my chronological age of 76.1.
 
Looks like I did a good job picking my ancestors!
 
Either that or 3 weeks of CaAKG works wonders.
 
Here is an interview with the TruAge creator
https://biohackstack...s/truage-index/

 
It's clear from the interview that even if everything he says is true and was competently done, TruAge is a (grossly underpowered and narrowly-ranged) surrogate for chronological age, not  biological age (which is what we're interested in). If there's a delta between your chronological age per the calendar and per the clock, that's mostly just telling you about the error in the clock.
 

I asked the study's author. The answer was somewhat ambiguous.
 
https://www.longecit...ndpost&p=898406

 
I don't think it's ambiguous at all: he says it's a bad idea, and for sensible reasons. See also my posts on arginine alpha-ketoglutarate in this context.
 

I'm a little confused:
 according to the label, one serving (2 tablets) of Rejuvant contains 100% of the RDA of preformed Vitamin A. Why?
To get the effect size that the mice study implicated, one would need to take 17 to 30 servings per day. This sound like an uncomfortable amount of preformed Vitamin A - toxicity is a real issue.

 
 As I mentioned in a prior post, Kennedy has tested numerous such combinations, and these are the most promising ones by gender. They're assuming you're only going to take the suggested serving size of 2 tabs; if you (rightly, I agree) think a higher dose is more realistic for translation, you need an outside source.
 

Is there is a source for affordable Ca-Akg without Vitamin A, so that everyone can take 17 gram every day? Otherwise there is no evidence that it is indeed life extending (certainly not with that amount of Vitamin A in Rejuvant)?

There's the Simplesea solution (not the pill with MCFA) and the Kirkman; Oakman identified anohter vendor selling powder, but as I mentioned they look questionable (not that I have much faith in Simplesea, either).

[albedo]

...
It's clear from the interview that even if everything he says is true and was competently done, TruAge is a (grossly underpowered and narrowly-ranged) surrogate for chronological age, not  biological age (which is what we're interested in). If there's a delta between your chronological age per the calendar and per the clock, that's mostly just telling you about the error in the clock....

 

Yes, but I would not throw the baby out with the water of the bath ... precisely that delta could be not only "noise" but includes a "signal" which I would guess reflects the heterogeneity of the aging phenotype, heterogeneity increasing when cross sectionaly one studies populations at different classes of age.
 

[yz69]

 

It's clear from the interview that even if everything he says is true and was competently done, TruAge is a (grossly underpowered and narrowly-ranged) surrogate for chronological age, not  biological age (which is what we're interested in). If there's a delta between your chronological age per the calendar and per the clock, that's mostly just telling you about the error in the clock.
 

 

Hi Michael, 

 

Why TruAge  is a (grossly underpowered and narrowly-ranged) surrogate for chronological age, not  biological age?  What test do you think is a good one for testing biological age?  

 

Thanks!

 

 

[TMNMK]

In any case, vitamin A is largely useful, pleiotropic

 

"DNA hypermethylation at imprinted loci has been reported in the progeny of mice deficient in Tet1 and Tet2 (Dawlaty et al., 2013), and vitamin C maintains active histone marks (H3K4me2/3) and prevents the DNA hypermethylation and silencing of imprinted genes at the Dlk1-Dio3 gene cluster (Stadtfeld et al., 2012). Vitamin C can also work synergistically with other factors, such as Vitamin A (retinoic acid, RA), to enhance mouse iPSC reprogramming (Esteban et al., 2010; Schwarz et al., 2014; Hore et al., 2016). RA has no direct effect on TET enzymatic activity but can increase TET expression levels, leading to increased 5hmC and increased DNA demethylation (Hore et al., 2016). When supplemented in combination, vitamin C enhances the activity of an increased pool of TET protein driven by RA signaling, resulting in greater reprogramming efficiency of primed mouse ESCs to naïve pluripotency (Hore et al., 2016)." Reprogramming the Epigenome With Vitamin C 2019 Taylor Lee Chong, Emily L. Ahearn, Luisa Cimmino 10.3389/fcell.2019.00128 Frontiers in Cell and Developmental Biology

 

Bizarre that Brian Kennedy didn't include vitamin C in the patent, perhaps that prior art. Given that they're shooting for TET, TET being aKG-dependent dioxygenases.

Edited by TMNMK, 28 February 2021 - 12:39 AM.

[Guest]

@TMNMK:

 

EVERY Vitamin is useful. The point was, that overdosing on Vitamin A is a problem. The in-vitro studies you are quoting don't change that.

 

Vitamin A is fat-soluble vitamin. It is in circulation much longer than water soluble Vitamins. Rejuvant contains 100% of the RDA for Vitamin A. We have studies in living humans (not mice cells in a dish) demonstrating long term liver damage, if you take about 10 times the RDA of Vitamin A for a prolonged duration. And if you want to have the mice effects you need to take more than the single serving of Rejuvant on their label (the mice consumed up to 30 times the amount, scaled for humans).

 

 

@yz69:

 

I can't speak for Michael, but given his connection to the SENS-F I'd assume the following:

 

"aging" is the manifestation of functional decline and pathologies, that results from the accumulation of cellular and tissues damage over decades

 

 

Reversing the methylation patterns does nothing for reversing the accumulated damage. It may or may not influence the accumulation of future damage (there is not much in-vivo data on that). But reversing some methylation patterns by 50% doesn't repair your damaged mitochondria, it doesn't reverse the plaque you already got in your vascular system or the cross-links of proteins.

 

Methylation changes are not the major drivers of aging. They do not constitute the functional decline of pathologies, that commonly are summarized as "aging". They are indirect measures of the progress in time of a living metabolism  - and they might well respond to or influence the speed of accumulation of the damage, that results in an "aging phenotype".

 

But those clocks are not the aging phenotype itself. That is the damage. And reversing the clocks doesn't reverse the damage. That's what all the SENS strategies are about. You have mtDNA damage. You got damaged proteins. Your body doesn't have the machinery to deal with that. No amount of methylation reversal changes that. E.g. you are not suddenly able to break up lipofuscin to make autophagy work like in a young person. Humans just don't got the enzymes to do the clean-up.

Edited by Guest, 28 February 2021 - 08:28 AM.