It’s no secret that a healthy diet can fight several diseases and promote overall well-being. But there are other benefits when you avoid too many calories. In a first-of-its-kind randomized controlled trial, an international team of researchers led by the Butler Columbia Aging Center at Columbia University Mailman School of Public Health, shows that calorie restriction can also slow aging in healthy adults.
How Calorie Restriction Affects the Aging Process
In worms, flies, and mice, calorie restriction can slow biological aging processes and increase healthy lifespans. In the study, the researchers wanted to test whether calorie restriction also slows down biological aging in humans. The Phase 2 randomized controlled trial CALERIE™, funded by the US National Institute on Aging, is the first to evaluate the effects of long-term calorie restriction in healthy, non-obese people. The study randomized 220 healthy men and women at three US sites 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.
To measure biological aging in participants in the CALERIE study, the team analyzed blood samples collected from study participants before the intervention and after 12 and 24 months of follow-up. Because people live very long lives, it’s impractical to follow them until differences in age-related diseases or survival appear, the experts say. Instead, the researchers rely on biomarkers designed to measure the pace and progression of biological aging over the duration of the study. The team analyzed methylation marks on DNA extracted from white blood cells. DNA methylation marks are chemical marks on the DNA sequence that regulate the expression of genes and are known to change with age.
In the primary analysis, they focused on three measurements of DNA methylation dates, sometimes known as “epigenetic clocks.” The first two, the PhenoAge and GrimAge clocks, estimate biological age, or the chronological age at which a person’s biology would appear “normal”. These measurements can be thought of as “odometers” that provide a static measure of how much aging a person has experienced. The third measure the researchers looked at was DunedinPACE, which estimates the pace of aging, or rate of biological deterioration, over time. DunedinPACE can be thought of as a “speedometer”. In contrast to the results for DunedinPace, there were no effects of the intervention on other epigenetic clocks. The difference in results suggests that dynamic pace-of-aging measures such as DunedinPACE may be more sensitive to the effects of the intervention than static biological age measures.
Slower Aging and a Reduction in Mortality Risk
The CALERIE™ intervention slowed the pace of aging as measured by participants’ blood DNA methylation using the DunedinPACE (Pace of Aging, Computed from the Epigenome) algorithm. The intervention effect on DunedinPACE was a 2 to 15 percent slowdown in the aging process, which in other studies resulted in a 10 to 15 percent reduction in mortality risk, an effect similar to a smoking cessation intervention.
The results of the studies show that calorie restriction slows aging in humans. But calorie restriction isn’t for everyone. The researchers stress that the results are important because they provide evidence from a randomized trial that slowing down human aging may be possible. They also give a sense of what effects the researchers might look for in studies of interventions that might appeal to more people, like intermittent fasting or time-restricted eating.
Follow-up of study participants is ongoing to determine if the intervention had any long-term effects on healthy aging. In other studies, a slower DunedinPACE has been associated with a reduced risk of heart disease, stroke, disability and dementia. The study on the after-effects of the CALERIE™ intervention will test whether the short-term effects observed during the study result in a longer-term reduction in age-related chronic diseases or their risk factors.