This phase 2 randomized controlled trial is the first investigation of the effects of long-term caloric restriction in healthy, non-obese humans. The study randomly assigned 220 healthy men and women to a 25% caloric restriction or a normal diet for two years.
CALERIE, acronym in English of Comprehensive evaluation of the long-term effects of reducing energy consumptionshowed a slowdown in the rate of aging measured from the blood DNA methylation of the participants using the algoritmo DunedinPACE (Pace of Aging, Computed from the Epigenome). A 2% to 3% decrease in the rate of aging translates into a 10% to 15% reduction in mortality risk, an effect similar to a smoking cessation intervention. The results are published online in the journal “Nature Aging.”
“In worms, flies, and mice, caloric restriction can slow the biological processes of aging and prolong healthy life,” says lead author Daniel Belskybut now our work shows that caloric restriction also delays biological aging in humans.
To measure biological aging in trial participants, Belsky’s team analyzed blood samples collected from trial participants before the intervention and after 12 and 24 months of follow-up. “Humans live a long time,” Belsky explained, “so it’s not practical to follow them until we see differences in diseases related to aging or survival. Instead, we trust developed biomarkers to measure the rate and progress of biological aging over the duration of the study.”
Specifically, this team analyzed the methylation marks in the DNA extracted from white blood cells. The DNA methylation marks they are chemical tags in the DNA sequence that regulate gene expression and are known to change with aging.
In a first analysis, Belsky and his colleagues focused on three measurements of DNA methylation data, sometimes known as ‘epigenetic clocks’. The first two, the watches PhenoAge y GrimAgeestimate biological age, or the chronological age at which a person’s biology would appear “normal.”
These measures can be considered as odometers or odometers, which provide a static measure of the aging that a person has experienced. The third measure studied was DunedinPACE, which estimates the rate of aging, or the rate of biological deterioration over time. DunedinPACE can be thought of as a ‘speedometer’.
The study found evidence that caloric restriction slows the rate of aging in humans.
In contrast to the results of DunedinPaceno intervention effects were observed on other epigenetic clocks,” explains Calen Ryan, a research scientist at Columbia’s Butler Aging Center and co-senior author of the study.
For Ryan, “the study found evidence that caloric restriction slows the rate of aging in humans. But caloric restriction probably won’t work for everyone,” she acknowledges.
In any case, he stresses, the findings are “important because they provide evidence in a randomized trial that it is possible to delay human aging. They also give us an idea of the effect types that we might look for in trials of interventions that might appeal to more people, such as intermittent fasting or time-restricted eating.”
The study is ongoing and trial participants are currently being followed up to determine if the intervention had long-term effects on healthy aging. In other studies, orn Slower DunedinPACE is associated with a reduced risk of sickness heart disease, stroke, disability and dementia.