There is certainly no shortage of claims these days about “anti-aging” therapies. Spend a few minutes on social media and you’ll encounter confident assertions that a particular supplement, diet, drug, or infusion can make you biologically younger. While many of these claims are intriguing, separating enthusiasm from evidence has become increasingly difficult.
So, I was excited to read a new comprehensive review published in Frontiers in Genetics that attempts to bring some much-needed scientific rigor to this conversation. Rather than relying on anecdotes, Dr. Adiv Johnson and Dr. David Sinclair systematically analyzed 41 human intervention studies that measured the effects of various treatments on what are known as next-generation epigenetic aging clocks. And the results are both encouraging and cautionary.
But first, let me explain what epigenetic clocks are and what they reveal. Our DNA contains the genetic code we inherit from our parents. But sitting on top of that DNA are tiny chemical tags called methyl groups. These tags don’t change the genes themselves; instead, they influence whether genes are turned on or off.
As we age, predictable changes occur in these DNA methylation patterns. By examining hundreds or even thousands of these methylation sites across the genome, researchers can estimate a person’s biological age, which may differ from their chronological age.
Imagine two 65-year-olds. One exercises regularly, maintains metabolic health, sleeps well, and avoids smoking. The other has obesity, diabetes, chronic inflammation, and hypertension. Although both are 65 chronologically, their methylation patterns may suggest that one has a biological age of 58 while the other resembles someone in their seventies.
The earliest methylation clocks were designed simply to predict chronological age. The newer “next-generation” clocks go much further. They were specifically trained to predict outcomes that actually matter, including mortality risk, disease risk, inflammation, and overall health. This makes them potentially far more useful in evaluating interventions and therefore, powerful research tools.
And an important note: a change in an epigenetic clock does not necessarily prove that someone has become healthier or will live longer.
The investigators identified interventions that appeared to improve, worsen, or have no measurable effect on these next-generation aging clocks.
Simplified Summary of the Findings
| Intervention | Overall finding |
| Regular endurance exercise | Consistently favorable |
| Plant-rich diet | Favorable |
| Caloric restriction | Favorable |
| Omega-3 fatty acids | Favorable across several studies |
| Multivitamin/multimineral supplement | Modest benefit |
| Semaglutide (GLP-1 agonist) | One of the strongest positive findings |
| Pitavastatin | Favorable in one study |
| Metformin | Mixed results depending on the population studied |
| Ketamine | Small positive effect in limited studies |
| Umbilical cord plasma | Some favorable findings, very preliminary |
| Rapamycin | No significant effect in available human studies |
| Nicotinamide riboside | No significant effect |
| Senolytics (dasatinib/quercetin/fisetin) | No significant effect |
| Plasmapheresis | Unexpectedly worsened several aging clocks |
One of the strongest pharmaceutical findings involved semaglutide, Ozempic® which lowered several independent epigenetic aging measures and slowed the pace of biological aging in a randomized trial involving patients with an HIV-associated issue.
Among lifestyle interventions, several familiar recommendations performed well. Exercise, plant-rich dietary patterns, caloric restriction, and omega-3 fatty acid supplementation all showed favorable effects in at least some studies. Multivitamin supplementation also produced modest improvements in two commonly used aging clocks in a study of nearly 1,000 healthy older adults.
Interestingly, not every longevity intervention held up.
Rapamycin, nicotinamide riboside, folic acid, greens-based supplements, and senolytic combinations failed to significantly improve next-generation aging clocks in the available human trials.
One aspect of this review that I found especially refreshing is that it highlights something we often forget in longevity research: negative studies are just as important as positive ones.
Too often, excitement builds around promising laboratory findings or animal studies before adequate human research has been completed. Here, the investigators systematically evaluated what has actually been demonstrated in people, not mice, not isolated cells, but human clinical studies.
Perhaps even more interesting is that the interventions with the strongest evidence are largely the same ones we already recommend for improving metabolic health.
- Exercise.
- Healthy dietary patterns.
- Weight control.
- Omega-3 fatty acids.
- Caloric moderation.
These are hardly glamorous or novel interventions, but they repeatedly emerge as approaches to favorably influence biological aging across multiple independent measures.
A healthy dose of perspective
It’s tempting to interpret a reported reduction of four or five “biological years” as meaning someone has literally become younger. That would be inappropriate.
The authors repeatedly caution that these effect sizes represent changes in mathematical models, not direct measurements of lifespan or healthspan. They explicitly note that we do not yet know how closely these clock changes translate into future disease risk or longevity.
Nonetheless, these clocks represent one of the most exciting developments in aging research. Instead of waiting decades to determine whether an intervention extends human lifespan, scientists may eventually be able to use these and other validated biological aging markers to evaluate therapies much more rapidly. But we’re not quite there yet.
But this review provides an important reality check. Some interventions appear promising. Others, despite considerable publicity and social media hype, currently have little supporting human evidence. And perhaps most reassuring of all, the interventions with the strongest overall support remain the foundational lifestyle choices that improve virtually every aspect of human health.
So, your fountain of youth probably isn’t hiding in a single pill, technology or infusion. It may still look remarkably similar to what decades of good medical science have been telling us all along.
