Can Supplements Slow Aging? Large Epigenetic Study Reveals Surprising Clues

 

Can a supplement make the body biologically younger?

That is one of the most exciting — and controversial — questions in aging research. Chronological age moves forward at the same speed for everyone. Biological age does not. Some people reach their 70s with strong metabolism, resilient tissues, and low disease burden. Others show signs of accelerated aging much earlier.

This difference has pushed scientists to search for measurable signs of aging inside the body. One of the most powerful tools is the epigenetic clock, which reads DNA methylation marks that change with age. These clocks may help researchers test whether lifestyle, drugs, or supplements can slow biological aging without waiting decades for lifespan data.

A 2026 study by Pabis and colleagues, published in Aging Cell, used this strategy to examine supplement and medication use in 4,260 health-conscious individuals who purchased saliva-based epigenetic age tests. The study found that two supplements — delayed-release alpha-ketoglutarate, or dAKG, and coenzyme Q10, or CoQ10 — were associated with lower biological age.

The findings are intriguing, but not definitive. They do not prove that these supplements reverse aging. Instead, they provide a strong reason to test them in controlled clinical trials.

Methodology and Study Design

Cohort Composition and Recruitment

The researchers studied people who purchased TruAge saliva-based epigenetic tests between 2020 and 2025. This was not a typical general-population cohort. These were health enthusiasts — people already motivated enough to track biological aging and often experiment with supplements.

Compared with the general U.S. population, this group was healthier. Only 4% reported smoking, compared with 18% in NHANES. Only 12% reported fair or poor health, compared with 25% in NHANES. Supplement use was also very high: 71% of participants reported taking supplements.

This unusual feature made the cohort scientifically valuable. Many longevity-related supplements are rarely used in the general population, making them difficult to study. In this cohort, enough people were taking uncommon supplements to allow meaningful statistical analysis.

The Epigenetic Clock

The study used a saliva-based epigenetic clock developed by TruMe Labs. The clock measured DNA methylation at nine CpG sites selected for strong age-related patterns.

Across 4,260 participants, the clock showed good agreement with chronological age, with a mean absolute error of 5.36 years and a Pearson correlation of 0.86. This is notable because saliva testing is easier and more scalable than blood-based testing.

The researchers mainly used “Age Residual” rather than simple biological age minus chronological age. This was important because older participants tended to appear biologically younger relative to their chronological age, possibly due to survivor bias or clock-design effects.

Statistical Approach

The authors analyzed 84 supplement and medication categories. They first performed univariate comparisons, then corrected for multiple testing. Promising candidates were tested in multivariable models adjusted for sex, smoking, health status, physical activity, sleep, alcohol use, stress, ethnicity, recruitment source, and country.

They also used matching analyses to compare similar users and non-users, especially for dAKG. A smaller longitudinal group with repeated tests allowed the researchers to ask whether biological age improved over time.

Results and Scientific Interpretation

Validation of the Biological Age Instrument

Before looking at supplements, the researchers tested whether the clock reflected known health risks.

It did.

Smoking was associated with 3.53 years of increased biological age. Poor sleep added 0.84 years. Poor self-rated health was linked to a 5.20-year increase. People in the healthiest decile appeared about 4.4 years biologically younger than those in the least healthy decile.

This supports the idea that the clock was capturing meaningful biology, not just random methylation noise.

Supplement Users vs. Non-Users

Supplement users appeared biologically younger than non-users. However, this finding must be interpreted carefully. People who take supplements may also exercise more, eat better, sleep better, avoid smoking, and seek preventive healthcare.

This “healthy user bias” is difficult to remove completely, even with statistical adjustment.

Still, the finding suggests that supplement-rich health enthusiast cohorts may be useful for identifying candidate interventions worthy of formal clinical testing.

Cross-Sectional Supplement Findings

Alpha-Ketoglutarate (AKG) and Delayed-Release AKG (dAKG)

The strongest supplement signal came from delayed-release alpha-ketoglutarate.

AKG is a central metabolite in the Krebs cycle, but its role extends far beyond energy metabolism. It also supports amino acid metabolism, collagen biology, hypoxia signaling, and epigenetic regulation. Importantly, AKG is a cofactor for enzymes involved in DNA and histone demethylation, placing it directly at the intersection of metabolism and epigenetic aging.

In the study, 143 participants reported using delayed-release AKG. After matching, dAKG users had a 1.27-year lower Age Residual compared with matched non-users. The association remained significant in adjusted models.

The studied product, Rejuvant, is not simple AKG. It is a delayed-release calcium-AKG formulation combined with vitamin A for men or vitamin D3 for women. This matters because delayed release may improve delivery to the intestine and circulation.

The finding is biologically plausible, but it also requires caution. One of the senior authors has a commercial relationship with the company producing Rejuvant. That does not invalidate the study, but it makes independent replication essential.

Coenzyme Q10 (CoQ10)

CoQ10 showed a different pattern. It was not the strongest cross-sectional signal, but it stood out in the longitudinal analysis.

CoQ10 is a mitochondrial electron carrier and antioxidant. Because mitochondrial dysfunction is a hallmark of aging, CoQ10 is an attractive candidate for influencing biological age.

Participants taking CoQ10 at baseline were almost twice as likely to show improvement in Age Residual over time. This is interesting because mitochondrial restoration may require sustained supplementation before measurable effects appear.

However, CoQ10 has not consistently extended lifespan in rodent studies. Its potential benefits in humans may be more related to mitochondrial function, cardiometabolic health, or oxidative stress than simple lifespan extension.

Medication Findings

The medication analysis was limited because only 456 participants reported drug use.

Antithrombotic drugs such as aspirin, warfarin, and clopidogrel showed associations with lower biological age in unadjusted analyses. Statins and blood pressure medications also trended in a favorable direction.

One unexpected signal came from antihistamines, which ranked highly for lower biological age measures, although the finding did not survive multiple-testing correction. This may be worth further study because histamine signaling and chronic inflammation are increasingly linked to aging biology.

Interestingly, no clear benefit was observed for rapamycin, metformin, or GLP-1 agonists. This should not be interpreted as evidence that these drugs lack geroscience value. The study was likely underpowered for these medications, and users may have had underlying conditions that confounded the results.

Longitudinal Analysis

Among 755 participants with repeated epigenetic tests, more people showed improvement than worsening in Age Residual. This may reflect healthy lifestyle behavior, regression to the mean, or both.

The dAKG longitudinal analysis was limited by small user numbers. Subscription-based analysis suggested possible benefit, but significance weakened after adjusting for baseline Age Residual.

CoQ10 was the most consistent longitudinal signal, suggesting that its potential effect may develop gradually over time.

Strengths and Limitations

Key Strengths

The study’s biggest strength is its unique cohort. Health enthusiasts are not representative of the general population, but they are highly useful for studying uncommon supplements.

The study also used multiple statistical approaches, including correction for multiple comparisons, multivariable adjustment, matching, and longitudinal testing.

Another strength is the use of saliva-based epigenetic testing, which could make large-scale biological age studies more accessible.

Critical Limitations

The study is observational. It cannot prove causality.

Healthy user bias remains a major limitation. Supplement users may differ from non-users in many ways that cannot be fully measured.

The commercial connection involving the dAKG product also requires caution.

The epigenetic clock itself is another limitation. It is a first-generation clock trained mainly on chronological age, not mortality risk or disease outcomes. This may make it less sensitive to true intervention effects.

Supplement use was self-reported, and the study lacked detailed dose, frequency, and duration data. This is important because biological effects depend heavily on exposure.

The cohort was also predominantly Caucasian, limiting generalizability.

Broader Scientific Context

The Epigenetic Clock as a Research Tool

This study shows how saliva-based epigenetic clocks could be used to rapidly screen possible anti-aging interventions in large populations.

As epigenetic clocks become more sensitive and clinically validated, they may become powerful tools for identifying which interventions deserve randomized controlled trials.

AKG in the Longevity Landscape

AKG has become an increasingly interesting molecule in aging research because it connects metabolism, inflammation, epigenetics, and tissue function.

The current study supports the idea that delayed-release AKG may be associated with lower biological age, but the effect size is modest and must be tested independently.

Randomized trials, including the ABLE trial, will be critical for determining whether AKG truly slows biological aging in humans.

CoQ10 and Mitochondrial Aging

CoQ10’s longitudinal signal fits well with the biology of mitochondrial aging. If mitochondrial decline contributes to biological aging, then restoring mitochondrial electron transport and antioxidant defense could plausibly improve age-related physiology.

However, stronger clinical studies are needed to determine whether CoQ10 changes epigenetic age, improves healthspan, or simply marks a healthier user population.

Conclusions

This study provides an important real-world look at supplements, medications, and biological aging in a large health enthusiast cohort.

The most notable findings were that delayed-release AKG and CoQ10 were associated with lower biological age measures. These signals are biologically plausible and consistent with known roles in metabolism, mitochondrial function, and epigenetic regulation.

But the findings should be viewed as hypothesis-generating, not practice-changing. The study does not prove that AKG or CoQ10 reverses aging. It shows that these compounds deserve more rigorous testing.

The larger message is clear: biological age testing may become a useful tool for identifying promising longevity interventions. But the future of this field will depend on well-designed randomized trials, not supplement enthusiasm alone.

Reference

Pabis, K., W.Wang, K.Selvarajoo, et al. 2026. “Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals.” Aging Cell25, no. 6: e70517. https://doi.org/10.1111/acel.70517.

Image credit: Portions of the figure in this article were generated using ChatGPT (OpenAI) or Google Gemini.

Disclaimer: This blog post is intended solely for educational and scientific informational purposes. Any mention of therapeutic drug names, including FDA-approved medications, is for the purpose of accurate reporting and discussion of biomedical research and does not constitute medical advice, endorsement, or promotion. Readers should not interpret the content as a recommendation for any specific treatment. Always consult a qualified healthcare professional for medical advice or treatment decisions.

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