Change Your Diet, Change Your Lifespan: First Clinical Trial Of Its Kind Shows Nutrition and Lifestyle Program Reduces Biological Age By Over 3 Years

“You are what you eat.” This commonly used expression, suggesting that the foods we consume become a part of us and influence our health, is true, but may not tell the entire story. In addition to impacting things like body weight, appearance, and lab measurements, the foods we eat can alter how many years we live — and how many of those years are lived disease-free. This can be predicted by looking at biological age — the internal damage that accelerates aging and disease in our cells, tissues, and organs.

In a new clinical trial published in the journal Aging, Dr. Kara Fitzgerald and colleagues show how specific dietary and lifestyle changes impact biological age in a group of middle- to older-aged men. Remarkably, this short 8-week study reversed biological age by over 3 years, providing the first-ever evidence in a human trial that nutrition and lifestyle habits alone can turn back the aging clock.

Epigenetics: How Environment Alters Gene Activity 

Over the past decade or so, many longevity researchers have made it their mission to determine the best way to quantify biological aging — and how to slow it down or even reverse it. One such method of assessing this internal aging is by looking at the changes that occur to our DNA. A common form of this DNA modification is called methylation — the addition or removal of chemicals called methyl groups to strands of DNA. 

As one of the foremost researchers on this topic, Dr. Steve Horvath, discovered in 2013, DNA methylation patterns are a strong predictor of biological age. By assembling a large dataset of sites where DNA methylation changes occur with age — coined as DNAmAge (standing for ‘DNA methylation age’ — these biological clocks can predict with impressive precision how fast your insides are aging.

DNA methylation is a significant component of the field of epigenetics — the study of how gene activity changes in response to the environment, including diet, lifestyle, toxin exposure, stress, or UV radiation.  Although epigenetic changes are heritable and can be passed along from parent to child, these modifications do not change the actual DNA sequence. Instead, epigenetic changes — like DNA methylation — affect how our cells read the genes. 

However, DNA methylation in itself is neither good nor bad — both over- and under-methylation can be harmful. Rather, methylation can result in specific genes being turned on or off. Some genes we would prefer to stay “on,” like those that suppress tumor growth, while others, like inflammation-promoting genes, would be best turned “off.” However, with age or unhealthy lifestyles, our genes often do the opposite of what we would want.

Although there are 20 million or so methylation sites on the human genome, just a few thousand of them are highly correlated with aging, with about 60% of the sites losing methylation and 40% becoming over-methylated with age. Using this knowledge, Fitzgerald and colleagues designed a nutrition and lifestyle program with the goal of targeting these age-related methylation pathways. 

Promoting a Plant-Centered and Polyphenol-Rich Diet 

The research team guided a group of 43 relatively healthy men between the ages of 50 and 72 through an 8-week dietary intervention. The treatment was primarily centered around eating high amounts of plants and polyphenols — antioxidant compounds that modulate or support DNA methylation, referred to as “methylation adaptogens.” 

The study participants were instructed to eat foods high in the nutrients folate and vitamins A and C, as well as the polyphenolic compounds curcumin (found in turmeric), EGCG (found in green tea), rosmarinic acid (found in rosemary), and quercetin and luteolin, found in many fruits and vegetables. The most-encouraged “methylation adaptogen” foods were wild berries, beets, cruciferous vegetables (broccoli, cauliflower, kale), green tea, and herbs and spices.

They didn’t only eat plants, though — their diet also included moderate amounts of high-quality, nutrient-dense animal proteins, like eggs, liver, and grass-fed beef. Dairy and carbohydrates were restricted (no grains, added sugar, beans, potatoes, corn, or legumes), and two daily supplements were given — a fruit-and-vegetable powder and a probiotic to boost healthy gut bacteria. Lastly, the men were coached on sleeping 7 or more hours per night, moderately exercising 5 days per week, reducing stress with breathing exercises, and intermittently fasting from 7 pm to 7 am. 

Diet and Lifestyle Program Turns Back the Aging Clock

After following this healthy diet and lifestyle plan for 8 weeks, the men in the treatment group were an average of 3.23 years younger on their DNAmAge clocks compared to the control group. Those in the intervention group also had a 1.96-year average reduction from their own biological ages at the start of the study. Conversely, the men in the control group aged an average of 1.27 DNAmAge years throughout the study period. As Fitzgerald comments about the study, “These early results appear to be consistent with, and greatly extend, the very few existing studies that have so far examined the potential for biological age reversal.”

Notably, the intervention didn’t result in an increase or decrease in overall methylation. Instead, the diet program repositioned the methylation patterns to be more consistent with youth — some genes likely got turned back ‘on,’ while others switched ‘off. The men in the treatment group also experienced reductions in total and LDL (“bad”) cholesterol and triglyceride levels, which are risk factors for cardiovascular and metabolic diseases when elevated. 

The Future of Using Food to Reduce Epigenetic Age

With these impressive results, Fitzgerald and colleagues demonstrate for the first time how diet and lifestyle changes can reverse epigenetic age in a human clinical trial. As stated by author and epigeneticist Moshe Szyf, “This study provides the first insight into the possibility of using natural alterations to target epigenetic processes and improve our well-being and perhaps even longevity and lifespan."

Although there are some limitations — small sample size and the undiverse sample of older, mostly-white men — this study sets the stage for future research on turning back the biological clock without the use of pharmaceuticals. As researchers project that delaying aging and age-related disease by just 2 years could save $7 trillion over 50 years, these results could provide meaningful benefits — both for socioeconomic reasons and for personal health and well-being. 

Lead author Dr. Fitzgerald summarizes,  "What is extremely exciting, is that food and lifestyle practices, including specific nutrients and food compounds known to selectively alter DNA methylation, are able to have such an impact on those DNA methylation patterns we know predict aging and age-related disease. I believe that this, together with new possibilities for us all to measure and track our DNA methylation age, will provide significant new opportunities for both scientists and consumers." 

References: 

Fitzgerald KN, Hodges R, Hanes D, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021;13(7):9419-9432. doi:10.18632/aging.202913

Horvath S. DNA methylation age of human tissues and cell types [published correction appears in Genome Biol. 2015;16:96]. Genome Biol. 2013;14(10): R115. doi:10.1186/GB-2013-14-10-r115