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Scientists are trying to determine whether reducing calories could have beneficial effects on aging. Lightsy/Stocksy
  • A new study finds that reducing caloric intake may slow the pace of aging according to some biomarkers.
  • Participants in the study who reduced their caloric intake with a carefully constructed and monitored dietary program slowed their pace of aging, shown by certain epigenetic biomarkers, by 2–3% after two years.
  • Similar effects have previously been shown in some animal trials, although other such studies found a detrimental effect.

A new study investigates whether calorie reduction could be a way to slow down aging. In a first-of-its-kind, randomized, controlled human study, scientists have looked at a single biomarker to show it could.

In promising results, the researchers of a recent study found that reducing calories resulted in a 2–3% slowing of participants’ pace that some molecules attached to their DNA, or their epigenome ages.

The authors cite previous research that equates the 2–3% rate decrease to a reduction in mortality risk of 10–15%. This is similar to the risk reduction expected when a smoker quits smoking.

Exploring calorie reduction as a way to slow down aging is a test of the geroscience hypothesis. It suggests that by slowing down or reversing aging-related molecular changes, a person’s lifespan may be extended and they may be able to avoid serious chronic diseases.

The study is published in Nature Aging.

The study’s senior investigator Dr. Daniel W. Belsky, associate professor of epidemiology at Columbia Mailman School of Public Health, said:

“Our results are exciting because they suggest it may be possible to slow the pace of aging in humans. That opens a lot of doors to what we might be able to do in the years ahead.”

The researchers of the current study employed a precision calorie-reduction and assessment system called “CALERIE.” CALERIE is an acronym for “Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy.” It is very different from what one would find in a diet for weight loss based on reducing one’s intake of calories.

The authors note the study’s calorie reduction was carefully designed to lower energy intake without depriving participants of essential nutrients.

“This was a complicated intervention that involved teams of nutritionists and dietitians working with participants to design diets that worked and physicians monitoring participants’ health to ensure safety,” said Dr. Belsky.

The study’s trial took place at three sites, and initially involved 220 healthy men and women. Men were ages 21–50, and (premenopausal) women were ages 21–47. For two years, 145 participants were tasked with achieving a 25% calorie reduction in the CALERIE program compared to their baseline caloric intake level. Forty-five individuals served as a control group.

The number of individuals who finally completed the trial was 117 people in the CALERIE group and 68 in the control group.

To measure the effects of CALERIE, the researchers depended on three age biomarkers, or “aging clocks”: PhenoAge, GrimAge, and DunedinPACE. All are based on DNA methylation that can be measured in blood samples.

“Humans live a long time. So the biomarkers can give us a first hint of whether the intervention is having the effect we are interested in testing,” said Dr. Belsky.

Both PhenoAge and GrimAge claim to estimate a person’s chronological age based on their current biology. This would be the age at which they would be viewed as standard. DunedInPace, on the other hand, measures the rate at which a person is aging.

DunedInPace is something like an aging speedometer. PhenoAge and GrimAge are comparable to snapshots.

Dr. Matt Kaeberlein, professor and director of the Healthy Aging and Longevity Research Institute at the University of Washington Medicine, who was not involved in the study, said:

“It’s important to keep in mind that these measurements only report on a portion of biological aging, and are probably not a precise overall measurement of ‘biological age’ or the ‘rate of biological aging’.”

The study found that calorie reduction had an effect on the DunedInPace biomarker, but not on PhenoAge or GrimAge measurements.

It may be that two years is not long enough to manifest a measurable change in PhenoAge or GrimAge.

“For the static aging biomarkers we just don’t know how long we would need to intervene in order to see an effect. In small-scale and uncontrolled trials, some interventions have shown changes over short timescales, and others do not,” Dr. Belsky said.

Dr. Kaeberlein, however, expressed concern specifically about DunedInPace, which Dr. Belsky helped develop.

“While the DunedinPACE test provides valuable information, it is not yet widely accepted as a definitive measure of overall biological aging rate,” Dr. Kaeberlein pointed out.

“I think this is good suggestive evidence that caloric restriction can modify aspects of biological aging in humans, similar to what has been known in laboratory animals for many decades,” said Dr. Kaeberlein about the study.

He noted, however, that in animal tests, results have been uneven and that “roughly one-third of genetic backgrounds experience no positive effect on lifespan or have their lifespan shortened” by calorie reduction.

Dr. Kaeberlein also said that faith in the hypothesis that caloric reduction slows down aging is “not one that is shared by the field as a whole.”

“[A 25% reduction in caloric intake] is unlikely to have large effects on biological aging unless implemented over many years, which is likely not reasonable for most people.”
— Dr. Matt Kaeberlein

“It is also possible that the effects were small because only a subset of the population benefit[s] from this type of intervention,” he added.