Does Calcium-AKG (Rejuvant) make you 8 years biologically younger?
Claim attributed to Ponce de Leon Health (Rejuvant marketer), with co-author Brian K. Kennedy and mouse-study researchers at the Buck Institute.
The mouse evidence is real but modest and sex-limited; the human "8 years younger" headline rests on a single uncontrolled, sponsor-affiliated study using a commercial epigenetic clock. The controlled human test exists but has not yet reported.
Low-risk to take is not the same as proven to work; safety is a separate question from efficacy.
What it’s supposed to target
- Alpha-ketoglutarate (Krebs-cycle metabolite)
- Epigenetic / DNA-methylation enzymes
- mTOR + energy metabolism
- Inflammation
Alpha-ketoglutarate (AKG) is an everyday metabolite of the Krebs cycle, but it moonlights as a signaling molecule: it is a required cofactor for the enzymes that edit the epigenome (the dioxygenases that add and remove DNA and histone marks) and it nudges nutrient-sensing pathways such as mTOR. Its levels fall with age. The theory is that restoring AKG re-supplies those epigenetic enzymes and dampens age-related inflammation, in effect helping cells hold a more youthful gene-expression pattern.
The supporting evidence is lopsided. The strongest result is in mice, where late-life Ca-AKG compressed the sick period before death and modestly extended median lifespan, a real finding. The human headline, a roughly eight-year drop on an epigenetic-age clock, comes from a small, uncontrolled report of paying customers with no placebo group, run by the company that sells the product. An epigenetic-clock reading is a surrogate, not proof of slower aging, so a promising mouse mechanism is being marketed well ahead of any controlled human outcome.
Mechanism is theory, not proof. A plausible pathway explains why something might work, not whether it does. The verdict rests on the evidence below, not the elegance of the theory.
What would have to be true
A surrogate epigenetic clock would have to predict real health outcomes: unsettled (link not established).
The human result would have to come from a controlled design ruling out regression-to-mean and self-selection: fails (no control group).
Mouse benefits would have to translate to humans at human doses: untested (the ABLE RCT has not reported).
What the evidence actually shows
The mouse data are real, modest, and sex-limited
In the pivotal study (Asadi Shahmirzadi et al., Cell Metabolism 2020, n=183 mice, dietary CaAKG from 18 months), female mice gained a significant +16.6% median and +19.7% maximal lifespan, while the male increase (+9.6%/+12.8%) was not statistically significant. The Buck Institute press release frames the headline benefit as morbidity compression, with healthspan measures improved 'more than 40 percent' against roughly 12% average lifespan gain. This is a 'die healthier, not dramatically longer' result, in mice.
The human '8 years' claim rests on one uncontrolled study
The '8 years younger' figure traces to Demidenko et al. 2021 (Aging): a retrospective, open-label, non-placebo-controlled, non-randomized analysis of 42 self-selected Rejuvant customers (mean age ~63) using a commercial saliva clock (TruAge/TruMe) reading only 3 genes / 9 CpG sites. With no control group, regression-to-the-mean, healthy-user bias and self-selection cannot be excluded; the tiny p-value reflects within-group change, not a controlled effect. The data came from the marketer's own customers and senior author Kennedy is a paid consultant and board member of Ponce de Leon Health.
Studies, graded, and who paid
Peer-reviewed (Cell Metabolism 2020); robust ~40% healthspan gain, but lifespan effect modest and significant in females only. Author conflicts present.
One retrospective, open-label, non-controlled n=42 study on a 9-CpG commercial clock; sponsor-affiliated. Cannot establish causation.
No controlled human data on any hard outcome. Untested rather than disproven.
| # | Study | Type | Size | Funding / COI | Key limitations |
|---|---|---|---|---|---|
| 1 | Asadi Shahmirzadi et al., Cell Metabolism (mouse lifespan/healthspan) | Preclinical RCT in mice (n=183) | 183 mice | Industry-funded Author equity/board roles in Ponce de Leon Health; patents filed. Peer-reviewed. | Lifespan gain modest; significant in females only. Full text not directly accessible (403). |
| 2 | Demidenko et al., Aging (the '8-year' human study) | Retrospective, open-label, uncontrolled observational | 42 customers | Industry-funded Data from Ponce de Leon customers; testing by partnered lab TruMe; co-author on company board. | No control, no randomization, self-selected; 9-CpG surrogate clock. Cannot show causation. |
| 4 | Buck Institute press release | Institutional press release | na | , From institution employing some authors; magnitude framing only. | Not independent evidence; states human data still needed. |
| 5 | GlobeNewswire / Ponce de Leon press release | Corporate marketing communication | na | Industry-funded Issued for the product marketer. | Amplifies the n=42 study; not independent confirmation. |
| 6 | ABLE RCT protocol, GeroScience | Double-blind placebo-controlled RCT protocol | 120 planned | Mixed Academically run (Singapore/Netherlands) but study product supplied by Ponce de Leon; Kennedy on advisory board. | Results not yet published; small (n=120), short (6 months); surrogate endpoint. |
The whole human case depends on a commercial epigenetic clock as a stand-in for health; the field itself treats such clocks as easy to move and not validated against hard outcomes.
Unproven ≠ disproven
Unproven is not disproven: no controlled human trial has tested Ca-AKG's effect on aging, so the human claim is untested rather than refuted.
Where claim and evidence diverge
The gap is the leap from a modest, female-biased mouse result to a confident '8 years younger' human marketing claim built on an uncontrolled study.
The money trail
Every favorable human result is sponsor-affiliated: data from Rejuvant's own customers, testing by a commercially partnered lab, and a senior co-author who sits on the marketer's board.
Mouse-study authors held equity/board roles in Ponce de Leon Health; the '8-year' figure was launched via a corporate press release, not independent confirmation.
The honest read
Take the mouse data seriously as a reason to test AKG, not as proof it works in people. The human '8 years younger' figure is marketing, not evidence.
What would change this verdict
A pre-registered, placebo-controlled RCT (e.g. ABLE) showing a Ca-AKG advantage on a validated clock, ideally independent of the marketer.
Controlled human data showing reduced disease, frailty, or mortality, not just a shift in a surrogate marker.
Sources
- Asadi Shahmirzadi A, et al. Alpha-Ketoglutarate Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metabolism. 2020;32(3):447-456. PMID 32877690.
- Demidenko O, et al. Rejuvant... conferred an average 8 year reduction in biological aging on the TruAge DNA methylation test. Aging (Albany NY). 2021;13(22):24485-24499.
- Rhoads & Anderson. Alpha-Ketoglutarate, the Metabolite that Regulates Aging in Mice (commentary). Cell Metabolism. 2020. PMID 32877686.
- Buck Institute. Press release: a metabolite increases lifespan and compresses late-life morbidity in mice. Sept 2020.
- GlobeNewswire / Ponce de Leon Health. Study Shows Rejuvant Decreases Biological Age By Eight Years in Seven Months. Nov 30, 2021.
- Mkrtchyan G, et al. Alpha-ketoglutarate supplementation and BiologicaL agE (ABLE) intervention study protocol. GeroScience. 2023;45(5):2897-2907.
People also ask
- Does Calcium-AKG make you 8 years biologically younger?
- Unproven. The 8-year figure rests on a single retrospective, open-label, non-controlled study of 42 people using a commercial epigenetic clock, run by a sponsor-affiliated group. That design cannot establish causation, so the headline is marketing rather than evidence.
- Does Calcium-AKG extend lifespan in mice?
- Partly. A peer-reviewed 2020 Cell Metabolism study showed a robust roughly 40 percent healthspan gain, but the lifespan effect was modest and significant only in females. Author conflicts were present, so treat it as a reason to test AKG, not proof it works in people.
- Is there controlled human evidence for Ca-AKG?
- Not yet on any hard outcome. There is no controlled human data showing reduced disease, frailty, or mortality. A placebo-controlled trial exists but has not yet reported, so the human benefit is untested rather than disproven.
- Who funds the Rejuvant longevity studies?
- Every favorable human result is sponsor-affiliated. The data came from Rejuvant's own customers, testing used a commercially partnered lab, and a senior co-author sits on the marketer's board. The 8-year figure launched via a corporate press release, not independent confirmation.
Part of our guide: Longevity supplements, fact-checked
Caveat is journalism, not medical advice. We check public claims against published evidence; we don’t diagnose, treat, or tell you what to take.