Calorie Deficit Diet Delays Aging in Healthy Adults

A calorie deficit diet can reduce the aging process in healthy adults, according to a ground-breaking randomized controlled experiment conducted by an international team of researchers under the direction of the Butler Columbia Aging Center at Columbia University’s Mailman School of Public Health. Using the algorithm DunedinPACE, the CALERIE intervention reduced the rate of aging as shown by the participants’ blood DNA methylation (Pace of Aging, Computed from the Epigenome). According to other studies, the intervention’s impact on DunedinPACE was equivalent to a smoking cessation intervention in that it caused a 2-3% slowing of the aging process and a 10-15% reduction in mortality risk. The journal Nature Aging posts the findings online.

“In worms, flies, and mice, the calorie restriction can slow biological processes of aging and extend healthy lifespan,” says senior author Daniel Belsky, Ph.D., associate professor of epidemiology at Columbia Mailman School and a scientist with Columbia’s Butler Aging Center. “Our study aimed to test if calorie restriction also slows biological aging in humans.”

The effects of a prolonged calorie deficit diet on healthy, non-obese humans are being studied for the first time ever in the CALERIE Phase-2 randomized controlled trial. 220 healthy men and women were randomly assigned to a regular diet or a 25 percent calorie restriction for two years at three sites throughout the United States for the trial. Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy is abbreviated as CALERIE.

Belsky’s team examined blood samples taken from trial participants at the pre-intervention baseline and after 12- and 24-month follow-ups in order to quantify biological aging in CALERIE Trial participants. “Humans live a long time,” explained Belsky, “so it isn’t practical to follow them until we see differences in aging-related disease or survival. Instead, we rely on biomarkers developed to measure the pace and progress of biological aging over the duration of the study.” The team analyzed methylation marks on DNA extracted from white blood cells. DNA methylation marks are chemical tags on the DNA sequence that regulate the expression of genes and are known to change with aging.

Belsky and colleagues’ initial investigation concentrated on three measurements of the DNA methylation data, also referred to as “epigenetic clocks.” The PhenoAge and GrimAge clocks, which are the first two, calculate biological age, or the age in years at which a person’s biology would be considered “normal.” These measurements can be compared to “odometers” that offer a static assessment of the amount of aging a person has gone through. DunedinPACE, which gauges the rate of biological decline over time or the rate of aging, was the third measurement that the researchers looked at. You might imagine DunedinPACE as a “speedometer.”

“In contrast to the results for DunedinPace, there were no effects of the intervention on other epigenetic clocks,” noted Calen Ryan, Ph.D., Research Scientist at Columbia’s Butler Aging Center and co-lead author of the study. “The difference in results suggests that dynamic ‘pace of aging’ measures like DunedinPACE may be more sensitive to the effects of intervention than measures of static biological age.”

Our study found evidence that a calorie deficit diet slowed the pace of aging in humans” Ryan said. “But calorie restriction is probably not for everyone. Our findings are important because they provide evidence from a randomized trial that slowing human aging may be possible. They also give us a sense of the kinds of effects we might look for in trials of interventions that could appeal to more people, like intermittent fasting or time-restricted eating.”

The trial’s participants are currently being followed up on to see if the intervention had any long-term benefits on healthy aging. In other studies, a slower DunedinPACE was linked to a lower risk of dementia, heart disease, and stroke. According to Sai Krupa Das, a senior scientist and CALERIE investigator who is in charge of the long-term follow-up of CALERIE participants, “Our study of the legacy effects of the CALERIE intervention will test whether the short-term effects observed during the trial translated into a longer-term reduction in aging-related chronic diseases or their risk factors.”

Daniel Belsky and associates from the University of Otago and Duke University created DunedinPACE. Researchers used data from the Dunedin Longitudinal Study, a significant birth cohort study of human development and aging that tracked 1000 people born in Dunedin, New Zealand, in 1972–1973, to create DunedinPACE. To create a single composite measure of the Pace of Aging, researchers first examined the pace of change in 19 biomarkers over the course of 20 years of follow-up. The 20-year Pace of Aging was then reduced into a single time point DNA methylation blood test using machine learning techniques. The DunedinPACE algorithm produces values that represent the years of biological aging experienced within a single year, giving a measurement of the rate of aging.

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