Studies suggest that calorie restriction may slow down the pace of aging in healthy adults by reducing oxidative stress and inflammation, improving metabolic function, and enhancing cellular repair mechanisms. However, further research is needed to fully understand the mechanisms behind these effects and to determine the optimal level and duration of calorie restriction for promoting healthy aging in humans.
An international team of researchers led by the Butler Columbia Aging Center at the Columbia University Mailman School of Public Health found that caloric restriction can slow the rate of aging in healthy adults in a first-of-its-kind randomized controlled trial. The CALERIETM intervention slowed the rate of aging as measured by blood DNA methylation using the DunedinPACE algorithm (Pace of Aging, Computed from the Epigenome). The intervention effect on DunedinPACE represented a 2-3% slowing in the rate of aging, which translates to a 10-15% reduction in mortality risk in other studies, an effect similar to a smoking cessation intervention. The findings have been published online in the journal Nature Aging.
“Calorie restriction can slow biological processes of aging and extend healthy lifespan in worms, flies, and mice,” says senior author Daniel Belsky, Ph.D., associate professor of epidemiology at Columbia Mailman School and scientist with Columbia’s Butler Aging Center. “We wanted to see if calorie restriction slows biological aging in humans.”
The CALERIETM Phase-2 randomized controlled trial, funded by the National Institute on Aging in the United States, is the first study of the effects of long-term calorie restriction in healthy, non-obese humans. For two years, 220 healthy men and women were randomly assigned to either a 25% calorie restriction or a normal diet at three sites in the United States. CALERIE™ is an acronym for ‘Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy’.
Our research found that calorie restriction slowed the rate of aging in humans. However, calorie restriction is likely not for everyone. Our findings are significant because they provide evidence from a randomized trial that it is possible to slow human aging.
Calen Ryan
Belsky’s team analyzed blood samples collected from CALERIE Trial participants at the pre-intervention baseline and after 12- and 24-months of follow-up to assess biological aging. “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 track the rate and progression of biological aging over the course of the study.” The researchers looked at methylation marks on DNA extracted from white blood cells. DNA methylation marks are chemical tags on the DNA sequence that regulate gene expression and are known to change with age.
In the primary analysis, Belsky and colleagues focused on three measurements of the DNA methylation data, sometimes known as “epigenetic clocks”. The first two, the PhenoAge and GrimAge clocks, estimate biological age, or the chronological age at which a person’s biology would appear “normal”. These measures can be thought of as “odometers” that provide a static measure of how much aging a person has experienced. The third measure studied by the researchers was DunedinPACE, which estimates the pace of aging, or the rate of biological deterioration over time. DunedinPACE can be thought of as a “speedometer”.
“In contrast to the results for DunedinPace, there were no effects of an 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 research found that calorie restriction slowed the rate of aging in humans,” Ryan said. “However, calorie restriction is likely not for everyone. Our findings are significant because they provide evidence from a randomized trial that it is possible to slow human aging. They also give us an idea of the kinds of effects we might look for in trials of interventions that might appeal to a wider range of people, such as intermittent fasting or time-restricted eating.”
The trial participants are now being followed up on to see if the intervention had any long-term effects on healthy aging. Slower DunedinPACE has been linked to a lower risk of heart disease, stroke, disability, and dementia in other studies.
“Our study of the CALERIETM intervention’s legacy effects will test whether the trial’s short-term effects translated into longer-term reductions in aging-related chronic diseases or their risk factors,” says Sai Krupa Das, a senior scientist, and CALERIE investigator who is leading the long-term follow up of CALERIETM participants.
Daniel Belsky and colleagues at Duke University and the University of Otago created DunedinPACE. DunedinPACE was developed using data from the Dunedin Longitudinal Study, a landmark birth cohort study of human development and aging that follows 1000 people born in Dunedin, New Zealand, in 1972-73. The researchers first looked at the rate of change in 19 biomarkers over a 20-year period to create a single composite measure of the Pace of Aging. The researchers then used machine learning techniques to reduce this 20-year Pace of Aging to a single-time-point DNA methylation blood test. The DunedinPACE algorithm values correspond to biological aging years experienced in a single calendar year, providing a measure of the rate of aging.
