Fitzgerald · Aging 2021 · randomized controlled trial · n=43

Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial.

Cited 371 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 33844651 · doi:10.18632/aging.202913 · record verified 2026-08-28

What was done

Forty-three healthy adult males aged 50–72 were enrolled in an 8-week randomized controlled clinical trial. The intervention group received guidance on diet, sleep, exercise, and relaxation, along with supplemental probiotics and phytonutrients, while the control group received no intervention. Genome-wide DNA methylation was assessed from saliva samples with the Illumina Methylation Epic Array, and biological age was calculated using the 2013 online Horvath DNAmAge clock.

What was found

The diet and lifestyle intervention was associated with a 3.23-year decrease in DNAmAge compared to controls (p = 0.018). Within the intervention group, DNAmAge decreased by an average of 1.96 years from baseline to the end of the program (p = 0.066). Significant changes in blood biomarkers included a 15% increase in mean serum 5-methyltetrahydrofolate (p = 0.004) and a 25% decrease in mean triglycerides (p = 0.009).

Why it matters

This pilot trial provides initial randomized evidence that a combined diet and lifestyle program can favorably alter DNA methylation age clocks in older men.

Limits

The sample size was small (n = 43) and limited exclusively to healthy males aged 50–72. The study duration was brief (8 weeks), the control group received no intervention rather than an active or sham control, DNA methylation was measured only in saliva, and clinical health outcomes were not evaluated.

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