Study Finds Potential Reversal of Epigenetic Age with Diet and Lifestyle Changes

Having an advanced age is the largest risk factor for impairde mental and physical function and many non-communicable diseases including cancer, neurodegenerative diseases, type 2 diabetes, and cardiovascular disease. 

DNA methylation is the addition of a methyl group to cytosine residues at selective areas on a chromosome. This process can readily and cheaply be mapped from tissue samples. Of 20+ million methylation sites on the human genome, there are a few thousand at which methylation levels are tightly correlated with age. Currently, the best biochemical markers of an individual’s age are all based on patterns of methylation. 

In a study published in 2021 in the journal Aging, researchers evaluated how diet and different lifestyle changes could influence epigenetic age. 

Study Results and Development 

The best-studied methylation-based clock according to the researchers is the multi-tissue DNAmAge clock, which can predict all-cause mortality and multiple morbidities better than chronological age. 

One commonly used tissue for evaluation of methylation is saliva, which can be considered a good source of high-quality DNA, containing both white blood cells and buccal cells. This was the method used to determine methylation levels. The dietary recommendations used in the study were based on biochemistry and generalized measures of health. 

The study was a randomized controlled trial that included a total of 43 healthy adult males between ages of 50-72. The treatment included a 8 week program with dietary changes, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. 

Diet and Lifestyle Modifications

The diet modification was plant-centered, but included a high intake of nutrients that are substrates or cofactors in methylation pathways (folate, betaine), and polyphenolic modulators (curcumin, rosmarinic acid). The diet also restricted carbohydrates and included mild intermittent fasting to lower glycemic cycling, and was supplemented with a daily fruit and vegetable powder and a probiotic providing 40 million CFU of Lactobacillus plantarum 299v. 

Lifestyle changes included a minimum of 30 minutes of exercise per day, at least 5 days per week at an intensity of 60-80% maximum perceived exertion. Previous studies have shown that exercises such as tai chi are associated with slowing of age-related DNA methylation losses. One study on 647 women with a lifelong history of exercise was associated with a similar endpoint.

Twice-daily breathing exercises that elicit the Relaxation Response were prescribed for stress reduction. It also included a recommendation of at least 7 hours of sleep per night. 

DNA methylation clock

When compared to participants in the control group (20), participants in the treatment group scored an average 3.23 years younger at the end of the 8 week program according to the Horvath DNAmAge clock. 

Twice-daily breathing exercises that elicit the Relaxation Response were prescribed for stress reduction.


The results of the study demonstrate the potential reversal of epigenetic age with diet and lifestyle changes and that they can reduce the biological aging in individuals otherwise known to be healthy. 

Once again the importance of a balanced diet, proper nutrition and physical activity are shown.


Kara N. Fitzgerald, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging. 2021; 13:9419-9432. 

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