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Can you slow biological aging? What randomized trials have actually shown

Can you slow biological aging? What randomized trials have actually shown

Specialty Testing Guide › TruAge Biological Age Testing

Possibly, by a small amount. The best evidence so far comes from a two-year randomized trial in which cutting calories slowed one pace-of-aging measure by about 2 to 3 percent. A few other trials report small shifts in clock scores, and none has yet shown that those shifts lead to less disease or longer life.

So the honest answer is that biological aging measures can move, the moves seen in good trials are modest, and the habits that reliably lower your risk of heart disease, diabetes and cancer are still the ones to focus on.

Key takeaways

  • Randomized trials, not before-and-after stories, are the fair way to judge whether anything slows a clock.
  • In the CALERIE trial, two years of eating less nudged DunedinPACE down slightly but left several other clocks unchanged.
  • Effects in the larger trials are measured in months over several years, not in years reversed.
  • No trial has yet linked a slower clock to fewer heart attacks, cancers or deaths in the same people.

Why trials matter more than testimonials

Clock scores bounce around from one test to the next because of technical noise, shifts in blood cell mix and short-term illness. If you test, change your diet and test again, a lower number may be real, or it may be noise.

A randomized trial solves that problem by comparing a treated group with a similar untreated group over the same period. That is why this article focuses on trials, and why small, short or uncontrolled studies deserve caution.

The CALERIE trial: calorie restriction

CALERIE randomized 220 healthy adults without obesity to a goal of eating 25 percent fewer calories, or to their usual diet, for two years.1 Most people in the restriction group managed less than the target, averaging close to 12 percent.

When researchers later measured DNA methylation in stored blood samples, the restriction group showed a slower DunedinPACE, a reduction in pace of aging of about 2 to 3 percent. The same intervention did not significantly change PhenoAge or GrimAge, two widely used clocks.1 Responses also varied: some participants slowed much more than average, while others sped up.

The authors called the effects small and said longer follow-up is needed to know whether they translate into less disease. The trial also enrolled only healthy younger and middle-aged adults, men aged 21 to 50 and women aged 21 to 47, so its results do not automatically apply to older adults.

The DO-HEALTH trial: omega-3, vitamin D and exercise

In a later analysis of 777 older adults in the DO-HEALTH trial, a daily omega-3 supplement slowed three clocks slightly over three years, and omega-3, vitamin D and a home exercise program together had an additive effect on PhenoAge. The size of the benefit was about three to four months of biological aging over three years.2

That is a real signal in a well-run trial, but it is small. It does not show that any supplement prevents disease or extends life, and it is not a reason to start one without talking to your clinician.

Smaller and earlier studies

A pilot trial of 43 healthy men aged 50 to 72 tested an eight-week diet, sleep, exercise and relaxation program. It reported a clock age about 3 years lower than in the control group, measured in saliva with a first-generation clock. The authors themselves called for larger and longer trials to confirm it.3

Results like this are interesting, but a short study, a small group and an older clock in a different tissue make the finding fragile. Technical noise alone can produce differences of several years between repeat measurements on some clocks.4

StudyWhat was testedWhat changed
CALERIE (220 adults, 2 years)Eating less, goal of 25 percent fewer caloriesDunedinPACE about 2 to 3 percent slower; PhenoAge and GrimAge not significantly changed
DO-HEALTH (777 older adults, 3 years)Omega-3, vitamin D, home exerciseSmall slowing on several clocks, about 3 to 4 months
Pilot trial (43 men, 8 weeks)Diet and lifestyle programFirst-generation saliva clock about 3 years lower than controls

What this means for you

If you are thinking about a biological age test to track a new routine, set realistic expectations. A good trial result is a shift of a few percent in pace, or a few months in clock age, over years. A single retest after a few weeks cannot reliably show that.

The habits with the strongest evidence for a longer, healthier life are not new: not smoking, staying active, keeping a healthy weight, treating high blood pressure, blood sugar and cholesterol, and keeping up with cancer screening. A clock can be one more input. It should not replace those.

Next step

To understand the measure that moved in CALERIE, read DunedinPACE explained. To decide when a retest makes sense, see how often to retest biological age, or start at the biological age testing hub, which explains how testing works through our Conshohocken clinic.

Frequently asked questions

Can any treatment reverse my biological age?

Some small studies report lower clock ages after a program or treatment. Larger randomized trials show much smaller effects, and none has shown fewer diseases or deaths as a result. Treat claims of dramatic reversal with caution.

Should I try calorie restriction to slow my clock?

Not on your own. CALERIE participants had intensive support from a study team, and the effect was small. If weight or metabolic health is a concern, a plan made with your clinician is safer and better studied.

How long before a lifestyle change shows up on a clock?

The trials above measured change over one to three years. Shorter intervals are more likely to pick up noise than real change.

Related reading

This article is for general education and is not medical advice. Decisions about testing and treatment should be made with your clinician. If you have severe symptoms, call 911. For a suspected poisoning, call Poison Control at 1-800-222-1222.

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About Dr. Kenneth Varano, D.O.
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YoungerMeMD is a physician-led practice in Anti-Aging, Functional and Preventive Medicine, and your care is delivered by our whole clinical team. That team works under Medical Director Kenneth Varano, D.O., who brings over 30 years in clinical medicine and more than 20 years in age management and functional medicine — using science-backed, patient-focused strategies that restore balance, vitality, and health longevity.

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Barbara Dougherty, MSN, CRNP, is a Board-Certified Family Nurse Practitioner and Certified Menopause Practitioner (MSCP) specializing in optimizing hormones, and improving cardio-metabolic health. 

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References

  1. Waziry R, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging 2023. PMID 37118425 · doi:10.1038/s43587-022-00357-y↩
  2. Bischoff-Ferrari HA, et al. Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. Nat Aging 2025. PMID 39900648 · doi:10.1038/s43587-024-00793-y↩
  3. Fitzgerald KN, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY) 2021. PMID 33844651 · doi:10.18632/aging.202913↩
  4. Higgins-Chen AT, et al. A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking. Nat Aging 2022. PMID 36277076 · doi:10.1038/s43587-022-00248-2↩
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