“Calorie restriction slows age-related biological processes and extends healthy life in nematodes, fruit flies and mice,” said Daniel Belsky, PhD, senior author of the study. “Our study set out to explore whether calorie restriction also slows biological aging in humans.”
Caloric Restriction (CR) can be defined simply as scientific dieting — cutting calories (energy) while ensuring that the body’s essential nutrients, such as protein, fatty acids, vitamins and minerals, are adequate. A series of animal studies on nematodes, fruit flies and mice have shown that calorie restriction does extend their lives.
A recent study led by the Butler Columbia Center on Aging at Columbia University’s Mailman School of Public Health in the US has shown that calorie restriction can slow the rate of aging in healthy adults.
The study was published Feb. 9 in the journal Nature Aging.
https://www.nature.com/articles/s43587-022-00357-y
The trial – the CALERIE™ Phase-2 Randomized Controlled Trial – is the first ever to investigate the effects of long-term calorie restriction on healthy, non-obese people. The trial randomly assigned 220 healthy men and women from three locations in the United States to either a “25 percent calorie restriction” or a “normal diet” for two years.
CALERIE™ is an acronym for Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy, Funded by the National Institute on Aging.
To measure biological ageing in participants in the CALERIE™ trial, Dr Belsky’s team analysed blood samples from participants at three time points: pre-intervention baseline, 12 months and 24 months after intervention. Dr Belsky explained: “Humans have long lives; It would therefore be impractical if we followed our subjects until we observed age-related disease or survival differentiation among them. Instead, we rely on developed biomarkers to measure the rate and process of biological aging during this study period.”
The team analysed methylation markers – chemical tags on DNA sequences that regulate gene expression and are thought to change with age – on DNA taken from white blood cells.
CALERIE™ Trial Overview:
DNA methylation clock and aging rate measurement
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In their initial analysis, Belsky and colleagues focused on three measures of DNA methylation data — sometimes called “epigenetic clocks.” The first two measures — PhenoAge clocks and GrimAge clocks — estimated the subjects’ biological, or physical, age; These two measures can be thought of as “odometers” that statically measure how much aging an individual has experienced. The third measure is called DunedinPACE: it estimates the rate of ageing, or biological degradation. DunedinPACE can be thought of as a speedometer.
“Contrary to the DunedinPace results, the intervention had no effect on other epigenetic clocks,” noted Calen Ryan, PhD, a research scientist at the Butler Center on Aging in Columbia and co-lead author of the study. “The difference in results suggests that dynamic ‘ageing rate’ measures such as DunedinPACE may be more sensitive to the impact of an intervention than static measures of biological age.”
Dr Calen Ryan, a research scientist at the Butler Center on Aging in Columbia and co-lead author of the study, noted: “Contrary to the results measured by DunedinPace, long-term calorie restriction had no effect on the first two epigenetic clocks. These differences suggest that dynamic ‘aging rate’ measures such as DunedinPACE are more sensitive to long-term calorie restriction than static biological age measures.”
The study is now following up the subjects to determine if long-term calorie restriction has a long-term effect on healthy aging. Other studies have linked slower DunedinPACE to a reduced risk of heart disease, stroke, disability and dementia. “In this study, we will look at whether the short-term effects observed during this trial lead to a long-term reduction in age-related chronic diseases or other risk factors,” said Sai Krupa Das, senior scientist and investigator leading the long-term follow-up of the CALERIE™ study.
DunedinPACE was developed by Daniel Belsky and researchers from Duke University in the US and the University of Otago in New Zealand. To develop DunedinPACE, researchers analyzed data from the Dunedin Longitudinal Study, a landmark birth cohort study of human development and aging, It tracked 1,000 individuals born in Dunedin, New Zealand, between 1972 and 1973. First, the researchers analyzed the rate of change in 19 biomarkers over 20 years of follow-up to come up with a comprehensive measure of aging.
Next, the researchers used machine learning to extract 20 years of follow-up results into a single point assay of DNA methylation blood tests. The DunedinPACE values correspond to the number of years of biological aging experienced in a single calendar year, thereby providing a measure of the rate of aging.
Peer review
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Neil Mabbott, Professor of Immunopathology at the Roslin Institute, University of Edinburgh: “Data from this study of 200 healthy, non-obese adults showed that a reduction in dietary calorie intake of about 25% over two years coincided with changes in DNA in blood cells, which the authors estimated translated into a modest reduction in the rate at which their bodies aged. While the decrease in calorie intake appears to have slowed the rate of aging, it is important to note that this has not translated into an increase in life expectancy.”
“In designing interventions that may improve aging, it is important that they do not simply extend life span, but rather increase healthy life span or the duration of healthy living without chronic and age-related diseases. Further research is now needed to determine whether calorie restriction can similarly increase healthy life span and improve the duration of healthy aging.”
Dr Duane Mellor, registered dietitian and senior lecturer at Aston Medical School, Aston University, said: “While interesting, it is important to be cautious about encouraging particularly older people to simply reduce their food intake in order to slow down ageing. In older adults, maintaining a healthy weight, being physically active and eating a varied and healthy diet with enough protein can reduce the risk of falls.”
Professor Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow: “In the context of a small calorie reduction trial, this seems to be a very well done study exploring complex markers. But do we really need proof that eating fewer calories slows down the aging process? This is evident from national data sets – which show that people from Japan are thinner than most people and live among the longest in any country. There is also evidence in trials that drugs that help reduce ‘cellular overnutrition’ by removing excess sugar calories can also reduce many age-related outcomes, such as heart failure or chronic kidney disease. So this new work fits into an emerging body of evidence that all points in the same direction.”