Cutting Calories to Add Years Finally, we have evidence that caloric restriction may increase human lifespan.

Restricting calories in rats, dogs, and other animals leads to longer lifespans. But in a frustrating puzzle for scientists, we hadn’t yet shown the same is true for humans, even though lower calorie intake can decrease our risk of cancer. Now, scientists at Columbia University say they have early evidence that links eating less to longer lifespans.

Using data from the CALERIE phase 2 clinical trial, researchers tracked 220 healthy men and women aged 21–50—a control group that ate normally and a study group of people who were asked to cut calories by 25 percent for two years. They ranged in BMI from healthy weight to slightly overweight and participated in counseling sessions geared toward helping them make the shift. 

This reduction in the pace of aging cuts mortality risk by a whopping 10–15 percent, similar to the effect of smoking cessation.

“The study really shows that within a relatively short or moderate timeframe of two years, a behavioral intervention can actually change the pace of aging,” says Calen Ryan, one of the lead authors of the study, published this month in Nature Aging. Although participants averaged only a 12 percent caloric reduction, people on restricted diets still lowered their pace of aging by 2–3 percent as measured by DunedinPACE, an algorithm that tracks patterns of activity at a range of DNA methylation sites to determine the pace of aging. Based on current mortality predictions, that reduction in the pace of aging cuts mortality risk by a whopping 10–15 percent, “similar to the effect of a smoking cessation intervention,” Ryan says. 

Calorie restriction led to weight loss for some people in the trial, but Ryan says weight loss alone does not account for changes to the pace of aging. Even in pre-trial measurements, there was only a weak correlation between BMI and the rate of aging.

DunedinPACE is one of the latest DNA methylation trackers that scientists hope will speed longevity research. These measurements serve as a stand-in for actually measuring aging in longevity research—something that would literally take years and could balloon costs. Instead of waiting decades to determine the impacts of drugs or dietary changes on lifespan, epigenetic “clocks” track patterns of activity at DNA methylation sites, which govern gene expression, in order to measure biological age. A person with a healthy diet and exercise regime might have a biological age substantially lower than their actual age, while a sedentary smoker’s biological age would likely outpace the number of birthdays they’ve celebrated.

Puzzlingly, the changes scientists measured using DunedinPACE did not translate to a reduction in biological age using two earlier epigenetic clocks, GrimAge and PhenoAge. Yet a change in the pace of aging should ultimately lead to a lower biological age, according to Nick Webster, a research endocrinologist and expert in time-restricted eating at the University of California, San Diego. The reason could be differences in the construction of these tools.

“Some of the other clocks, due to their cross-sectional nature, might be reflecting the accumulated aging up to that point in life, more like an odometer, whereas DunedinPACE seems to be reflecting a pace of aging or a change in aging over time, more akin to a speedometer,” Ryan says. This could heighten the tool’s sensitivity to aging, but it’s not the only possible explanation.

“The fact that there was no effect of caloric restriction on those [earlier clocks] could just be that it wasn’t sufficient caloric restriction, or it wasn’t done for long enough,” says Webster, who called the findings “incremental.” A longer study might show whether the changes in the rate of aging ultimately lead to lower biological ages, but Webster noted that such a long experiment could be impractical. 

Despite its limitations, the current study “opens the door and provides the proof of concept for the idea that other approaches—whether it’s time-restricted eating or intermittent fasting—might actually have similar benefits,” Ryan says. As a wave of next-generation epigenetic clocks offers insight into the impact of everything from fasting to pharmaceuticals on human health and longevity, the study adds another glimmer of hope that shifting what we eat—whether or not it leads to weight loss—can meaningfully impact longevity.

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