By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
What slows aging, really?
What slows aging, and what only promises to? We all want to age slowly, and the market is full of supplements, protocols and “revolutionary” treatments. A study published in August 2026 in the journal Nature Medicine pooled data from 51 intervention studies in humans. The researchers asked what actually moves our “biological clocks.” The answers are simple. Good nutrition, exercise and a few older prescription drugs do. Dietary supplements, for the most part, do not. And most of the interventions moved nothing at all.
How do you even measure aging?
The age on your ID card doesn’t tell the whole story. Two 60-year-olds can be in completely different biological shape. Think of the heart and blood vessels, muscle mass, metabolism and the immune system.
To measure that gap, researchers developed “epigenetic clocks.” These clocks are based on DNA methylation, tiny chemical tags on our genes that change with age, environment and health. From a single blood test, you can calculate a “biological age” and track it over time.
The advantage is clear. A biomarker can show change within months, instead of waiting decades for disease or death. But this is where the study’s real question begins: do these clocks respond to interventions at all?
What the researchers did
A team from Yale University, led by Dr. Raghav Sehgal and Prof. Albert Higgins-Chen, built a database called TranslAGE. It includes 51 intervention studies with methylation tests before and after, for a total of 3,128 blood samples. The researchers ran the same 16 epigenetic clocks and 94 additional markers on every sample. That way, they could compare drugs, diets, exercise, supplements and medical procedures using one method.
It’s important to understand what kind of study this is. It analyzes how the markers respond, and it is not a meta-analysis of clinical effectiveness. In other words, the question was “do the clocks respond?” and not “which intervention extends life?”
The big picture: most interventions changed nothing
Of the 51 interventions, 19 significantly lowered epigenetic age, and 13 of them held up after statistical correction. By contrast, 5 actually raised it (3 after correction). Twenty-six interventions, more than half, had no effect at all. In a world where “anti-aging” has become a brand, that finding matters in its own right.
What slows aging: diet and exercise
Lifestyle changes showed the most consistent responses. A Mediterranean diet, a low-carb diet, a low-fat diet and regular exercise all lowered aging markers. Moreover, all seven diets tested lowered the aging score for the skeleton and muscles. Six of the seven also lowered the metabolic and inflammation scores.
The Mediterranean diet stood out. Two versions of it, in healthy populations, shifted the same markers in the same direction in two separate studies. In addition, quitting smoking produced the largest drop of all, specifically in the lung aging score. You can read about combining types of exercise in my article on aerobic vs. strength training.
What slows aging: drugs we already know
The largest average effect came from the drug group: -0.093, compared with -0.039 for lifestyle. Only the drugs differed significantly from the other categories. These are older prescription drugs that no one developed to slow aging.
Metformin, a first-line drug for type 2 diabetes, lowered some of the most reliable clocks: SystemsAge, PCGrimAge and PCPhenoAge. The most notable effect appeared in the inflammation, brain and metabolic scores.
Anti-TNF treatments are biologic drugs that suppress inflammation, for example in rheumatoid arthritis and Crohn’s disease. They lowered nearly all of the second-generation markers, and the result repeated across different studies. This supports the idea that chronic inflammation is one of the engines of aging.
The database also included semaglutide, the active ingredient in Ozempic and Wegovy. The direct evidence for it comes from an analysis of a randomized trial in the journal Nature Communications. In the 32-week trial, 45 patients received semaglutide and 39 received a placebo. The drug slowed the pace of aging by 4.9 years per year according to PhenoAge, and by 3.1 according to PCGrimAge. It also slowed DunedinPACE by about 9%. However, the researchers hadn’t planned this analysis in advance, and it involved a unique population: adults with HIV and changes in fat distribution.
What happens after bariatric surgery
Gastric bypass surgery didn’t lower any reliable overall clock. At first glance, that looks like “no effect.” But when the researchers looked at individual body systems, the picture flipped. The metabolic aging score dropped clearly, with an effect size of 0.43.
This principle runs through the entire study. Quitting smoking improved the lungs, surgery improved metabolism and metformin affected inflammation. In other words, a treatment improves the system it was designed to fix. So an overall clock that doesn’t move doesn’t mean nothing happened.
Can a supplement slow aging?
The evidence on dietary supplements was limited and inconsistent. Here is a telling example. Two studies of the same product shifted the same markers, but in opposite directions. Senolytics, compounds meant to clear out “old” cells, also showed conflicting results across five studies.
A caveat is important here. The number of supplement studies was small. Also, replacing a vitamin or mineral when you’re deficient is real medical treatment. But treating a deficiency is one thing, and claiming that a supplement slows aging is another. At this point, that claim rests on belief, not data.
Not every biological clock measures the same thing
Perhaps the most practical finding concerns the measuring tool itself. First-generation clocks, trained to predict chronological age, mostly reflect random noise. By contrast, clocks trained to predict mortality or the pace of aging were sensitive and consistent.
DunedinPACE, a measure of the pace of aging, dropped significantly with 16 interventions and rose with only one. PCGrimAge showed the strongest statistical significance. In addition, DunedinPACE responded especially to lifestyle, while GrimAgeV2 responded especially to drugs. What does this mean if you’re considering a commercial biological age test? The number isn’t an absolute value like blood sugar or blood pressure. It depends on which clock the lab chose.
People who are sick respond more strongly
Of the 51 studies, 41 involved healthy people and 10 involved patients. The markers responded much more strongly in patients, probably because there was a lot to fix. So part of the “rejuvenation” may reflect successful treatment of a disease or of inflammation, rather than a reversal of aging. To me, that is exactly the message. Treating risk factors well is one of the most meaningful ways to influence how we age.
Before you rush to ask for a prescription
First, a change in a biomarker isn’t proof that aging has slowed. There’s still no agreed definition of a clinically meaningful change. According to the researchers, an effect size of about 0.2 roughly corresponds to one year of epigenetic age. However, we don’t know whether such a change translates into less disease or a longer life.
Second, many of the drug studies involved patients. Şebnem Ünlüişler of the London Regenerative Institute, who was not involved in the study, cautioned that the changes “may partly reflect improvement in the underlying disease.” In her view, they are not a reason for healthy people to take these drugs for anti-aging.
Third, the studies varied widely in age, duration and quality. Also, some of the authors are linked to a commercial epigenetic testing company that supplied part of the data.
Alongside the interventions tested here, researchers are also exploring experimental approaches, such as an enzyme that may repair proteins that have aged.
Bottom line: what slows aging
Sometimes advanced science brings us back to basics. Dr. Sehgal told Medical News Today that no single intervention has yet shown that it slows aging broadly. So the proven steps remain unglamorous: don’t smoke, exercise, eat well, sleep, and treat chronic conditions such as high blood pressure and diabetes.
In my experience in the clinic, that is exactly what works. Nutrition, physical activity and medical support, and when appropriate, medication or surgery. The new drugs are impressive, but they are a tool within a plan, not a substitute for one. In the end, what slows aging is consistent, evidence-based care for the body we have today.
The information in this article is general and does not replace personal medical advice. Please make any change in medication only in consultation with your doctor.
References
Responsiveness of epigenetic aging biomarkers to longevity interventions in humans
Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy
Can you slow the aging process? Study reveals which interventions might help
Longevity: What might actually help slow down aging?
Epigenetic biomarkers show promise for longevity, but which clock moves which needle?
Some of the authors of the Nature Medicine study are affiliated with TruDiagnostic, which supplied part of the data.
