A signal worth investigating, not a settled fact
In Singapore, researchers examining epigenetic data from more than 4,200 individuals have found that users of a delayed-release alpha-ketoglutarate supplement showed biological ages averaging 1.8 years younger than non-users — a finding that places an ancient metabolic molecule at the center of humanity's enduring search for ways to slow the passage of time within the body. The association held across demographics and persisted after accounting for lifestyle factors, yet longer-term tracking of the same individuals failed to confirm the effect with statistical confidence. Science here offers a tantalizing signal rather than a settled answer, reminding us that the distance between correlation and causation is where the most important questions live.
- A compound already present in every human cell is now being studied as a potential lever for reversing biological age, raising the stakes of what was once considered routine supplement research.
- The cross-sectional data is striking — 143 users of a specific dAKG product showed measurably younger epigenetic profiles even after controlling for smoking, weight, exercise, and alcohol consumption.
- The study's credibility is complicated by its own longitudinal arm, where following just 26 participants over time produced results too weak to be statistically meaningful.
- Researchers are candid about the gap between a compelling snapshot and the harder proof that only larger, longer studies can provide — and they are calling for exactly that.
- The broader sweep of the study found several other supplements — including CoQ10, curcumin, carotenoids, and NAD+ precursors — also associated with younger biological age markers, suggesting the question extends well beyond a single molecule.
Researchers at Singapore's National University of Medicine have published findings suggesting that a delayed-release form of alpha-ketoglutarate — known as dAKG — may slow biological aging. Drawing on epigenetic data from over 4,200 people who underwent commercial DNA testing between 2020 and 2025, the team found that users of a dAKG product called Rejuvant showed an average biological age reduction of 1.8 years compared to non-users.
The study examined 84 commonly used supplements and their relationship to biological age, measured through a metric called Age Residual derived from saliva-based epigenetic tests. Among the 143 Rejuvant users in the dataset, the biological age benefit held up after adjusting for smoking, weight, exercise, and alcohol intake, and appeared consistent across both men and women. Those who used dAKG on a regular subscription basis showed stronger effects than sporadic users.
The researchers were careful not to overstate their findings. A longitudinal analysis — tracking the same individuals over time — produced non-significant results, a limitation the team attributed in part to a very small subsample of just 26 participants. The gap between the cross-sectional promise and the weaker longitudinal signal is the study's central tension, and the authors acknowledge it openly.
The biological case for dAKG rests on its role in the citric acid cycle and its function as a cofactor in enzymes that regulate epigenetic markers. Animal studies have shown encouraging results, including reduced frailty and extended lifespan in older mice, though the evidence is not uniformly positive across species and conditions.
Beyond dAKG, the Singapore team found that carotenoids, calcium, CoQ10, curcumin, vitamin D3, and NAD+ boosters were also associated with lower biological age scores. The study, published in Aging Cell, represents one of the more systematic real-world examinations of supplements and epigenetic aging — but its authors are clear that larger, longer trials are needed before the promise of biological age reversal can be considered confirmed.
Researchers at Singapore's National University of Medicine have published findings suggesting that a delayed-release form of alpha-ketoglutarate—a compound known as dAKG—may slow biological aging. The study, which examined data from over 4,200 people who had undergone commercial DNA epigenetic testing between 2020 and 2025, found that users of a specific dAKG product called Rejuvant showed an average reduction in biological age of 1.8 years compared to non-users.
The research team, part of the Healthy Longevity Translational Research Programme, took a broad approach to their investigation. They looked at 84 commonly used supplements and their relationship to biological age—measured through a metric called Age Residual derived from saliva-based epigenetic tests. About 71 percent of the study participants reported using at least one supplement. Multivitamins and minerals dominated the landscape, used by 34.3 percent of the group, followed by vitamin D at 8.5 percent, omega-3 fatty acids at 6.5 percent, and joint support formulas at 5.4 percent. The researchers also examined NAD+ precursors like NMN and NR, along with berberine, carotenoids, creatine, and resveratrol.
When the team focused specifically on dAKG—the delayed-release calcium form of alpha-ketoglutarate—the results stood out. Among 143 users of Rejuvant, which contains dAKG along with vitamins A and D3, the biological age reduction held up even after researchers adjusted their analysis for factors like smoking status, overall health, weight, exercise frequency, and alcohol consumption. The benefit appeared consistent across both men and women. Notably, people who took dAKG as a regular subscription showed stronger age reversal than those who used it sporadically.
Yet the researchers were careful about their claims. When they conducted a longitudinal analysis—following the same people over time—the results weakened significantly. They attributed this partly to a small sample size of just 26 participants in that portion of the study. The cross-sectional snapshot showed promise, but the longer-term tracking did not yield statistically significant improvements. This gap between the two analytical approaches is precisely the kind of limitation that demands further investigation.
The biological plausibility of dAKG's effects rests on its role in cellular metabolism. Alpha-ketoglutarate sits at a crucial junction in the citric acid cycle and serves as a precursor for amino acid synthesis and collagen formation. It also acts as a cofactor in enzymes that modify epigenetic markers—the chemical switches that control gene expression without changing DNA itself. Animal studies have shown promise: in mice, plasma AKG levels decline with age, and calcium-AKG supplementation in older mice has been linked to reduced frailty and extended lifespan. In fruit flies, AKG extended survival on low-protein diets. However, not all animal research has confirmed these benefits, underscoring the uncertainty.
Beyond dAKG, the Singapore team identified other supplements associated with lower biological age markers. Carotenoids, calcium, CoQ10, curcumin, vitamin D3, and NAD+ boosters all showed associations with reduced Age Delta—another biological age measurement—after the researchers corrected for multiple statistical comparisons. The broader finding that supplement users as a group displayed younger biological ages than non-users suggests either that supplementation itself confers benefits or that people who take supplements tend to engage in other health-promoting behaviors.
The study appears in the journal Aging Cell and represents one of the larger efforts to systematically examine supplement use and epigenetic aging markers in a real-world population. Yet the researchers themselves acknowledge the central tension in their work: a striking cross-sectional association that did not translate into clear longitudinal evidence. That gap is not a failure of the research but rather an honest reflection of what remains unknown. The next phase will require larger, longer studies that follow supplement users over years, not months, to determine whether the promise of biological age reversal holds up under sustained scrutiny.
Citas Notables
dAKG was associated with lower biological age regardless of weight, weekly exercise volume or alcohol intake, with slightly larger benefits seen in those who exercise more often— Researchers in Aging Cell
A benefit on biological age is certainly plausible. Plasma AKG declines with aging in mice. AKG extends fly lifespan on a low protein diet and Ca-AKG supplementation late in life decreases frailty and extends mouse lifespan, although a later mouse study did not confirm this, highlighting the need for further research— Study authors
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So they found that people taking this dAKG supplement had biological ages 1.8 years younger. That sounds significant. But then the longer-term study didn't confirm it?
Right. The cross-sectional snapshot—a single point in time—showed a clear association. But when they followed people over time, the effect disappeared. It's the difference between a photograph and a film.
What could explain that gap? Are they saying the supplement doesn't actually work?
Not necessarily. They had only 26 people in the longitudinal arm, which is tiny. You can't draw firm conclusions from that. It could be a real effect that their study was too small to detect, or it could be that the cross-sectional finding reflects something else—maybe people who buy this particular supplement are already doing other things that slow aging.
Like what?
The researchers tried to account for exercise, weight, alcohol, smoking. But there are always unmeasured factors. People who buy a premium supplement product might have better healthcare access, lower stress, better sleep. The supplement itself might not be the active ingredient.
So should people be taking this?
That's the honest answer: we don't know yet. The biology is plausible—alpha-ketoglutarate does real work in cells. But plausible isn't proven. The researchers themselves are calling for more research. This is a signal worth investigating, not a settled fact.