Trials monitoring long-term calorie restriction showed a slowing down of biological ageing, with participants, who restricted their daily intake of food and drink by a quarter over two years, slowing their risk of dying by a significant 10%-15%.
Their pace of ageing slowed by 2%-3%, equal to a 10%-15% reduction in mortality, based on prior research, and similar to the benefits of quitting smoking.
“Our study shows that it may be possible to modify the pace of biological ageing through a behavioural intervention,” senior author and epidemiology professor Dan Belsky, from Columbia University in New York, told TimesLIVE Premium.
“There have been many trials of calorie restriction in adults with obesity, and a few short-term trials in healthy adults, (but) the CALERIE Trial is the first randomised controlled trial of long-term calorie restriction in healthy, non-obese human adults,” he said.
“In worms, flies and mice, calorie restriction can slow biological processes of ageing and extend healthy lifespan,” added Belsky, a scientist with Columbia’s Butler Aging Centre.
Rhesus monkeys, however, did not live longer after an extreme diet, a long-running study by the University of Texas found 10 years ago.
In the latest trial, 220 people from three sites in the US were randomised into two groups – those on a 25% calorie-restriction diet (relative to their baseline) or those on a normal diet – and had blood analysed before the trial launched, after 12 months and 24 months.
Columbia research scientist Calen Ryan, co-lead author of the study, notes that “calorie restriction is probably not for everyone”. Unlike daily life, trial volunteers had the monitoring of trained experts for two years.
Physicians who specialise in obesity-related diseases, most of which can be reversed with weight loss, say long-term data show it is hard to sustain weight loss over time. Only about 5% of people manage to control their weight effectively, long term, with lifestyle changes such as exercise and calorie restrictions, they observe.
For people to consume 25% fewer calories a day would be very difficult without medication or bariatric surgery, according to them.
Evidence has been growing in smaller and uncontrolled studies that restricting calories puts the brakes on ageing, and the latest data – from measuring participants’ blood DNA methylation, a molecular process associated with ageing – supports this trend.
“Humans live a long time,” said Belsky, “so it isn’t practical to follow them until we see differences in ageing-related disease or survival. Instead, we rely on biomarkers developed to measure the pace and progress of biological ageing.”
The international team found their intervention “slowed the pace of ageing” (measured by the DunedinPACE DNAm algorithm) but did not result in significant changes in biological age estimates (measured by DNAm clocks like GrimAge).
The study, published in Nature Aging, will show researchers what biomarkers to look for when other interventions, such as intermittent fasting, are investigated, Ryan said.
The team is following up with the CALERIE participants to investigate any long-term effects on healthy ageing. The trial name, CALERIE, stands for the comprehensive assessment of long-term effects of reducing intake of energy.
Senior scientist Krupa Das, the CALERIE investigator leading the follow-up, said they would test if the short-term effects last into a longer-term reduction in risks and age-related chronic diseases, such as diabetes.
Study details
Effect of long-term caloric restriction on DNA methylation measures of biological ageing in healthy adults from the CALERIE trial
R. Waziry, C. Ryan, D. Corcoran, K. Huffman, M Kobor, M Kothari, G Graf, S. Das & D Belsky et al.
Published in Nature Aging on 9 February 2023
Abstract
The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with ageing can delay or prevent multiple chronic diseases and extend healthy lifespan. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm), and is established to increase healthy lifespan in multiple species. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of ageing in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomised controlled trial in which n = 220 adults without obesity were randomised to 25% CR or ad libitum control diet for 2 yr. We found that CALERIE intervention slowed the pace of ageing, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of ageing can have profound effects on population health. The finding that CR modified DunedinPACE in a randomised controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies and contrasting with reports that biological ageing may not be modifiable. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality.
TimesLIVE article – Eat (much) less, live longer, major scientific study finds (Restricted access)
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