We really need a paper like the 900 days rule paper for studies that use clocks to separate really flimsy results from just merely flimsy results. Using more than 1 clock and using only 2 or 3rd generation clocks would be at the top of my list.
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I checked the paper, Kamil Pabis et al., âSupplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals,â Aging Cell, 21 May 2026.
https://onlinelibrary.wiley.com/doi/10.1111/acel.70517
Section 2.1 says the following:
âThis cohort study is based on a convenience sample mainly recruited online between 2020 and 2025. All participants had taken at least one TruMe saliva epigenetic age test (TruAge) and data was centrally stored at TruMe. Participants agreed to share their de-identified data for research purposes and approval for the study was granted under the protocol number NUS-IRB-2025-591. Participants were either referred by supplement and telehealth companies or they directly ordered tests via TruMe.â
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Yes⌠TruMe Labs⌠might have a TruAge test.
Link: https://trumelabs.com/?srsltid=AfmBOorcFCFBH_U0E-yIVQ9huBZ9M7q-6WeyE6J8S-4PsnCbqhspc_-k
But TruAge is a different test. Link: TruAge⢠Test
There you go.
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That link didnât work for me, but I have found the paper:
In this crossâsectional cohort we analyzed data from 4260 âhealth enthusiastsâ who purchased at least one salivaâbased DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9âCpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the general population. We tested the association between 84 commonly used supplements and biological age measured as Age Residual. In our crossâsectional analysis, a commercially available, delayedârelease calciumâalphaâketoglutarate (dAKG) + vitamin supplement (âRejuvantâ) was associated with an average 1.8âyear lower Age Residual. The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates. In contrast, participants who reported taking regular AKG showed a much smaller and statistically insignificant benefit. Among medications, there was a nonâsignificant benefit of antihistamine use, although the analysis was sampleâsize limited. In a longitudinal subset, intake of coenzyme Q10 (CoQ10) and dAKG was associated with increased odds of a lower Age Residual, but the results were not significant after multivariate correction. In conclusion, this study underscores the utility of an inexpensive salivaâbased epigenetic test for populationâlevel aging research and the benefits of health enthusiast cohorts. It highlights AKG and CoQ10, among others, as promising supplements warranting further investigation. Limitations like healthy user and recruitment bias remain and will require future controlled trials to fully address.
Now there is some clarity on the homeostasis of transcription it will be easier to theorise about the effects of additional AKG. I need to spend some time reading up on this, but I think it is in essence a sign of high levels of ATP available for transcription.
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I see. Thanks for letting me know.
I see that TruDiagnosticâs TruAge test is trademarked. TruMeâs is not.
Thanks, I fixed the link. I had accidentally included superfluous characters at the end. They are now gone in the edited post.
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Iâm curious, why donât you trust Trudiagnostic?
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Iâm seeing a lot of flip flopping and talking in circles in this chain without any discussion about two important points about alpha-ketoglutarate. Here are those two points -
- Alpha ketoglutarate is an essential co-substrate (aka fuel) for both TET (Ten-Eleven Translocation) enzymes and JmjC (Jumonji C domain-containing) histone demethylases. This means AKG helps fuel the processes that remove excess and aberrant methylation from DNA and histones. This removal of aberrant methylation then leads to improvements in gene expression. Theoretically, and increasingly backed by preclinical data, increased levels of AKG should lead to the upregulation of youth-associated genes and the silencing of age-associated genes. This process manifests as younger scores on epigenetic clocks, reduced systemic inflammation, and decreased frailty, as documented by the studies performed on akg so far. In my case, I have achieved an 8 year reduction in my OmicAge (one of the most predictive and comprehensive epigenetic clocks released to date) thanks in part to stacking liposomal ca-akg with liposomal vitamin C. Vitamin C is an enzymatic co-factor for the TET and JmjC (JMJD) enzymes .
2. The ITP tested plain AKG, not CA-AKG. Plain AKG has extremely low bioavailability because it broken down quickly during digestion, and the little that is absorbed has a low half life. For this reason akg is always sold bound to other molecules such as calcium or arginine. Most of the longevity research on akg has used ca-akg because it appears to have the longest half life. For some reason, which I donât understand, the ITP tested only plain akg. I believe this is the reason for the discrepancy between the ITPâs results and the results of other labs.
I think its important that we gain a deep mechanistic understanding of the supplements we take to make ourselves immune to marketing and also to recognize when research is valid or flawed.
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Let us emphasize again, this is a paper generated by people involved with a company that sells the compound being investigated. Thatâs fine. But now weâre told that a key differentiating characteristic of their super duper formulation, the thing that makes it work whereas all the others who donât have it donât work, the magic ingredient is⌠a âvitamin supplementâ. Oh, OK. Is it the early 1900âs all over again when vitamins were first discovered and all the rage miracle that was going to cure all diseases and keep us eternally young? Gee now that you gave this thing such a unique and powerful boost - vitamins - I can see how it makes all the difference. Hmm. So us poor slobs, who are careful to top off our vitamins and minerals, who definitely are on RDA and above, we need those extra vitamins from âRejuvantâ to make their magical potion work. Why, I can see how it makes all the difference, those who are fully dosed on all the vitamins need more vitamins. Science!
I think I will wait for some real trials by parties not involved in a commercial enterprise centered around the compounds in question. If you are convinced of the benefits of Rejuvant formulation - go right ahead. Iâll only note that this paper takes pains to point out that just taking AKG slow release or otherwise is worthless unless it comes with their vitamins. So - according to them - itâs Rejuvant AKG or bust. You take AKG, but not Rejuvant? Bust. Rejuvant or nothing. But go ahead. Iâll wait - the whole AKG thing seems thoroughly uninspiring, what with rodents that may or may not blah, blah, simple observation: what are the purported effect sizes? How inspiring are those noise adjacent âresultsâ? Oh well, to each their own.
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FWIWâŚ
'Rejuvant" is an overprice cheap product(tablets are the cheapest to manufacturer)that sell for premium plu$ price.
A waste of money in my view and opinion.
I take liposomal CA-AKG{3g, yes grams] mix with other compounds per day.
I donât take Rejuvant. I take a liposomal formulation of ca-akg for enhanced bioavailability and cellular uptake. Rejuvant doesnât make liposomal ca-akg.
I think its important that we be precise in what we are talking about here. I am talking about the chemical substance ca-akg, not Rejuvant. Rejuvant is one of many companies that sell ca-akg. I think Rejvuantâs claims that their ca-akg is somehow better than others donât stand up to scrutiny.
The fact that Rejuvant is engaging in shady marketing - (1) does not invalidate the biochemical mechanisms of akg with respect to the TET and JMDJ enzymes (which are well documented by many labs and are accepted science) and, (2) does not mean that ca-akg is an ineffective supplement.
I donât think we should hung up on Rejuvant. I think it would be much more productive if we discussed papers that shed light on the interesting and muti-faceted cellular mechanisms of akg. I also wanted to point out the discrepancy between the form of akg that the ITP tested (which is badly absorbed orally) and the form of akg (ca-akg) which most researchers use in their studies and which most longevity enthusiasts consume.
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Thatâs absolutely fine - learning about aging processes (or any processes) on a cellular level is very important. But thatâs all it is. To now claim that supplementing with something based on mechanistic speculation will result in a favorable health outcome is a whole other category of claim and invalid on its face. That extrapolation needs to be shown in outcome studies proving a measurable benefit in a rigorous trial in humans, or if you are a bit more of a gambler, at least in animal models (which is why we pay attention to ITP outcomes).
Looking at the mechanism and speculating about outcomes is a useful thing. A supplement based on just that is not a scientifically supportable proposition. Do we have well designed outcome studies of AKG in whatever formulation that show measurable health and longevity benefits in at least rodents, which were not conducted by people associated with Rejuvant? If not, then the whole AKG thing is currently of no practical application as a supplement.
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One question I have is: how do we determine that liposomal Ca-AKG has higher bioavailability than regular Ca-AKG? I havenât found any papers on this. Also, some papers show that low-dose AKG extends lifespan, while high-dose AKG accelerates aging. So is increasing bioavailability really a good thing?
https://www.sciencedirect.com/science/article/abs/pii/S246820202200016X
FWIWâŚ
This should be in a posting by itself as it gets burred in this thread.
Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)âintervention study protocol
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I looked at the paper. ITP also used Ca-AKG, the Calcium 2-oxoglutarate from Toronto Research Chemicals (TRC), using the exact same dosing protocol as the Cell Metabolism 2020 study. They just called it AKG in the main text, thatâs all. They couldnât possibly make such a basic mistake. The debate over whether Ca-AKG extends mouse lifespan can be put to rest. lol, that saves some people some money.
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This is not true. They DID test Ca-AKG. Not plain AKG.
Good digging, thanks for looking into that. In the body of the paper and in their charts they called it alpha ketoglutarate. Its only if you dig into the supplementary materials and look at the sourcing of the chemicals that they state they used ca-akg.
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