A recent study shows caloric restriction can slow biological aging in healthy adults, suggesting implications for long-term health and aging interventions.
Recent findings from a groundbreaking randomized controlled trial led by the Butler Columbia Aging Center at Columbia University indicate that caloric restriction can indeed slow biological aging in healthy adults. The study focused on the CALERIE™ intervention, which exhibited a 2-3% decrease in aging pace as measured by blood DNA methylation analysis through the DunedinPACE algorithm. This reduction correlates with a 10-15% lower risk of mortality, similar to benefits seen with smoking cessation.
“Previous research on model organisms like worms, flies, and mice suggested that calorie restriction has effects on aging processes and lifespan extension,” stated senior researcher Daniel Belsky, PhD, an epidemiology expert at Columbia Mailman School and a member of the Butler Aging Center. The primary goal was to ascertain whether similar effects can be observed in human subjects.
The CALERIE™ Phase-2 trial, supported by the US National Institute on Aging, marks the first in-depth investigation into long-term caloric reduction effects on healthy, non-obese adults. The study included 220 participants across three sites in the U.S., dividing them into groups with a 25% calorie-restricted diet versus a control group maintaining a normal caloric intake over two years. The acronym CALERIE™ stands for 'Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy.'
Biological aging in participants was assessed using blood samples taken at baseline and after 12 and 24 months. Explaining the rationale behind utilizing biological markers, Belsky noted, “Due to the prolonged lifespans of humans, it’s not feasible to directly measure changes in aging-related diseases or survival over time. We thus employed biomarkers that indicate biological aging “.
In their primary analysis, the researchers concentrated on three distinct measures within the DNA methylation data, often referred to as “epigenetic clocks." The first two, PhenoAge and GrimAge, estimate a person's biological age, providing a snapshot of how one’s biology compares to expected norms for their chronological age. DunedinPACE, in contrast, gauges the pace of aging over time—acting as a sort of speedometer for biological deterioration.
“Interestingly, while DunedinPACE showed significant changes in response to caloric restriction, the other epigenetic clocks did not exhibit any effects,” explained Calen Ryan, PhD, a research scientist and co-lead author of the study. This discrepancy hints that dynamic measures like DunedinPACE may be more sensitive to dietary interventions compared to static biological age evaluations.
Ryan highlighted the implications of the findings: “We’ve shown evidence that caloric restriction can decelerate the aging process in humans, yet it’s not a universally suitable approach. These results pave the way towards understanding how we can manipulate other types of dietary interventions, such as intermittent fasting or time-restricted eating.”
A follow-up study of the trial participants is already underway to explore the long-term impacts of caloric restriction on healthy aging. Studies suggest that a lower DunedinPACE is associated with decreased risks for cardiovascular events, disability, and dementia. Senior scientist Sai Krupa Das emphasized that this ongoing research aims to ascertain whether short-term benefits from the CALERIE™ intervention translate into prolonged reductions in aging-related diseases and associated risk factors.
DunedinPACE was developed by Belsky along with colleagues from Duke University and the University of Otago, based on data from the extensive Dunedin Longitudinal Study. Researchers analyzed the progression of 19 biomarkers over two decades to create a composite measure of the pace of aging. Subsequently, advanced machine-learning techniques were applied to devise a one-time DNA methylation blood test, allowing a straightforward assessment of an individual’s biological aging rate within a given year.
The research was funded by several grants from the US National Institute on Aging and utilized resources from both the CALERIE Research Network and the Dunedin Study. Additional backing was provided to coauthors through various NIH grants, underscoring the collaborative effort in this significant study.
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