Alpha-ketoglutarate (AKG) and astaxanthin are two of the most popular longevity supplements, and neither extended lifespan in one of the toughest mouse tests in aging research.
A new paper in GeroScience (2026;48(3):3821-3830) reports results from the National Institute on Aging's Interventions Testing Program (ITP). Across eleven interventions, none significantly increased lifespan in male or female mice. Several of the compounds had looked promising in earlier work.
This does not prove these supplements are useless in people. It does show how easily an exciting early signal can fail to hold up.
What Is the ITP, and Why Does It Matter?
The ITP is widely treated as a gold standard for testing lifespan-extending compounds in mice. It has two main strengths:
- Multi-site design. Identical experiments run at three sites: The Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center at San Antonio.
- Genetically heterogeneous mice. The UM-HET3 mice are a genetically varied population, which makes the results less dependent on the quirks of a single inbred strain.
That is a stricter standard than many single-lab studies, which can be swayed by one strain, one facility, or one unusually long-lived control group.
What Was Tested
The paper evaluated eleven interventions, a mix of new agents and previously tested compounds given at new doses or later starting ages. The named compounds were:
- Astaxanthin
- Meclizine
- Mitoglitazone
- Pioglitazone
- Alpha-ketoglutarate
- Mifepristone
- Methotrexate
- Atorvastatin combined with telmisartan
The abstract does not give exact doses, group sizes, or treatment durations for each compound. Those details are in the full text, which is open access (PMC13356140). I have not filled them in here.
The Headline Finding: Nothing Extended Lifespan
Despite earlier evidence of benefit in other models or under other conditions, no compound significantly increased lifespan in either sex.
That includes AKG. Earlier mouse work, including studies of calcium AKG, had generated considerable excitement and helped drive its popularity as a supplement. The ITP found no lifespan benefit under its conditions.
It also includes astaxanthin, mitoglitazone, and meclizine, all previously linked to lifespan extension within the ITP. When the researchers tried different doses or later starting ages, the benefit did not appear.
The Twist: Some Compounds Looked Harmful in Females
In females, pooled data from all three sites linked astaxanthin, late-start mitoglitazone, and pioglitazone to significantly shorter lifespan.
The authors then noticed that control females at The Jackson Laboratory lived unusually long. That can make a treatment group look worse by comparison. When they reanalyzed using only the other two sites, astaxanthin dropped out, and only mitoglitazone and pioglitazone still showed a negative effect.
So the astaxanthin "harm" signal is probably a statistical artifact of an unusually long-lived control group, not a real toxic effect. The glitazone signal held up in the reanalysis, though it is still a mouse finding.
Why Might Promising Results Fail?
The authors point to two variables:
- Dose. A compound that works at one dose may do nothing at another.
- Starting age. Many interventions seem to work only if started early, and some may do nothing or worse when started later.
They also argue for caution with single-site or single-cohort findings. A striking result in one lab is a hypothesis, not a conclusion.
What This Means for You
- Temper your expectations. The strongest controlled lifespan test so far found no extension. Don't expect a longevity payoff.
- Don't panic. This was a mouse study. It does not show that either supplement is harmful to humans, and it doesn't test every dose, form, or starting age.
- Dose and timing remain open questions. The paper itself says these variables are critical, and the abstract does not give a human-translatable dose.
- Judge by other goals. If you take astaxanthin for something else, such as skin or eye health, this study neither supports nor refutes that use. It only addresses lifespan in mice.
Who might reasonably continue: people who are comfortable with the cost and tolerability, understand the evidence is thin, and aren't relying on the supplement to extend life.
Who should skip or be cautious:
- Anyone buying it mainly for a lifespan benefit.
- People on prescription drugs, who should check with a clinician first. This applies to all supplements.
- Anyone considering pioglitazone for "anti-aging." It is an approved diabetes drug, and the female mouse signal is a reason not to use it off-label for longevity.
Focus on the proven basics: regular exercise, adequate sleep, not smoking, moderate alcohol intake, a healthy diet, a healthy weight, and managing blood pressure, lipids, and glucose. These have far stronger human evidence than any supplement here.
The Bottom Line
Negative results like this are valuable. They correct early hype and show why replication, multi-site testing, and attention to dose and age matter. For now, AKG and astaxanthin have not earned a place as proven longevity tools. They are interesting compounds that failed a very demanding test.
This article summarizes a published abstract. It is not medical advice.
