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Alpha-Ketoglutarate in Longevity Research
Alpha-ketoglutarate extended lifespan in worms and mice, but no controlled human trial shows it slows aging. A plain guide to the animal data, the Rejuvant reports and their limits.
Content last updated . This page has not been medically reviewed.
Back to Longevity & Healthy AgingWhat exists in humans
- No lifespan or disease-outcome trials. A 2022 review concluded there were no recently published studies showing AKG treats aging or age-related disease in humans, and that clinical studies were still required. [1]
- The Rejuvant retrospective report (2021). A "retrospective analysis" of 42 people who had been taking an AKG-based commercial formulation for about 7 months looked at a DNA methylation "biological age" test taken before and after. The authors reported an average 8-year lower biological age. There was no placebo group, and the authors said placebo-controlled testing was required. [6] A company that tested these customers' samples had a service agreement with the product maker, and one author is a consultant and board member of that maker. [6]
- A larger cross-sectional study (2026). Among 4,260 people who bought a saliva-based epigenetic test, those who said they took the Rejuvant product had on average a 1.8 years lower "age residual" than others; people reporting plain AKG showed a much smaller, non-significant difference. The authors named healthy-user and recruitment bias as limits and called for controlled trials. [7]
Evidence level for slowing human aging: insufficient evidence. The "8 years younger" figure is a marketing claim built on a biomarker, not a measured health outcome. A change in an epigenetic clock does not show a person is healthier or will live longer. See epigenetic clocks and DNA methylation and biomarker changes vs meaningful health outcomes.
How to evaluate claims
Ask: was it a randomized trial with a placebo? Were people or only mice studied? Was a health outcome measured, or only a test score? Who paid for it? More in longevity supplement blends and product claims.Frequently asked questions
Does alpha-ketoglutarate extend human lifespan?
No human study shows this. Lifespan extension was reported in worms and mice. [2][3]
Did Rejuvant make people 8 years younger?
A retrospective report of 42 users with no placebo group found an 8-year lower score on a DNA methylation test. That is a biomarker, not proof of better health. [6]
Is the human evidence getting better?
A 2026 observational study of 4,260 people found a 1.8-year lower score for Rejuvant users, with the authors noting bias and asking for controlled trials. [7]
Who funded the mouse study?
It received US National Institute on Aging support, and several authors declared company shares and a patent application. [3]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
How to read the evidence labels
Labels used on this page: preclinical (cells/animals only), insufficient evidence and marketing claim. For the research field as a whole, see how we label evidence in longevity research.
What it is
AKG is an intermediate in the Krebs cycle, the series of chemical steps cells use to turn food into energy. A 2023 review describes it as an endogenous metabolite, meaning the body already makes it, and notes it is also involved in amino acid metabolism and in how genes are switched on and off. [1]What the animal studies found
- Worms (preclinical). In the roundworm C. elegans, AKG extended adult lifespan. It appeared to act by inhibiting ATP synthase (part of the cell's energy machinery) and the TOR pathway. It did not extend life in worms already on a restricted diet, which suggests it overlaps with the effects of dietary restriction. [2]
- Mice (preclinical). In 2020, a calcium salt of AKG given to C57BL/6 mice was reported to promote a longer, healthier life, with lower levels of inflammatory signals. The authors described this as "compression of morbidity", meaning less time spent frail. [3] The study declares financial interests: several authors are shareholders or board members of Ponce de Leon Health, and some are named on a patent application related to the finding. [3]
- Other mouse and rat work. Older mice given AKG had more bone mass and less bone loss [4], and AKG improved a brain-signaling measure in a mouse model of Alzheimer's disease. [5] These are single-model laboratory findings.
Why this cannot be carried over to people: mice and worms age far faster than humans and have different metabolism. See aging in mice, worms and humans and reading longevity studies.
Safety and regulation
References
- Alpha-Ketoglutarate dietary supplementation to improve health in humans. Trends in endocrinology and metabolism: TEM, 2022. PubMed abstract. Read 2026-10-22.
- The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature, 2014. PubMed abstract. Read 2026-10-22.
- Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell metabolism, 2020. PubMed abstract. Read 2026-10-22.
- Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nature communications, 2020. PubMed abstract. Read 2026-10-22.
- Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease. Aging cell, 2025. PubMed abstract. Read 2026-10-22.
- Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging, 2021. PubMed abstract. Read 2026-10-22.
- Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals. Aging cell, 2026. PubMed abstract. Read 2026-10-22.