Calorie Restriction Slows Aging in Human Trial

A randomized controlled trial has found that caloric restriction slows aging in adults. The study, led by researchers from the Butler Columbia Aging Center at the Columbia University Mailman School of Public Health, is published in Nature Aging.

The CALERIE™ trial

In animal models, calorie restriction can slow the biological aging process, extending the organism’s lifespan. “Our study aimed to test if calorie restriction also slows biological aging in humans,” says senior author Dr. Daniel Belsky, associate professor of epidemiology at Columbia Mailman School and a scientist with Columbia’s Butler Aging Center.

The CALERIE™ (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) Phase II trial evaluated the effects of a 25% calorie reduction (CR) below an individual’s baseline level over a 2-year period in 220 healthy men and women. The participants, aged between 21–51 years, were recruited across three sites in the United States and randomly assigned to undergo CR or a normal diet. Blood samples were collected at baseline, 12 months into the study and after 24 months follow up.

How do we measure aging?

“Humans live a long time,” says Belsky, “So it isn’t practical to follow them until we see differences in aging-related disease or survival.” Rather, the researchers utilize biomarkers – DNA methylation marks – found in the participants’ blood that have been developed to measure the pace and progress of aging over the course of the study.

Two “epigenetic clocks” – PhenoAge and GrimAge – were used to estimate biological age in the primary analysis. Biological age is distinct from chronological age in that it does not increase at the same rate for all individuals. Chronological age refers to how long a person has been alive, while biological age refers to the epigenetic alterations and DNA methylation processes that have occurred in a person’s cells; marks that are indicative of their level of deterioration.

The algorithm “DunedinPace” (Pace of Aging, Computed from the Epigenome), was the third measure in the study. Unlike epigenetic clocks, DunedinPACE estimates how quickly biological aging is occurring, likened to a “speedometer” by the researchers.

Pace of aging slowed by calorie restriction

Belsky and team found that the CR intervention did not have any impact on the epigenetic clocks, but slowed the pace of aging by two–three percent according to DunedInPACE. 

“In contrast to the results for DunedinPACE, there were no effects of intervention on other epigenetic clocks,” explains Dr. Calen Ryan, 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.”

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“Our study found evidence that calorie restriction slowed the pace of aging in humans” Ryan adds.  “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.”

To assess whether the CR intervention produced any long-term impacts on healthy aging, the researchers are conducting follow-up assessments of the study participants. “Our study of the legacy effects of the CALERIE™ intervention will test if the short-term effects observed during the trial translated into longer-term reduction in aging-related chronic diseases or their risk factors,” says Dr. Sai Krupa Das, a senior scientist and CALERIE investigator who is leading the long-term follow up of participants.

“This study enrolled people considered to be in the healthy weight range and those who were overweight, not people living with obesity.  It suggests that measures of ageing from DNA may slow, but does not report on any physical or functional changes in aging,” says Dr. Duane Mellor, a registered dietitian and senior lecturer at Aston Medical School. He adds that the results must be interpreted with caution and encourages individuals – especially older people – not to reduce their food intake with the goal of slowing aging. “In aging adults, maintaining a healthy weight, being physically active and eating a varied and healthy diet with enough protein is known to reduce the risk of falls.”

Reference: Waziry R, Ryan CP, Corcoran DL, 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. doi: 10.1038/s43587-022-00357-y.

This article is a rework of a press release issued by Columbia University. Material has been edited for length and content.