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Long-term Caloric Restriction can Slow the Pace of Aging

Lasse Damgaard Harreskov by Lasse Damgaard Harreskov
April 11, 2025
Reading Time: 4 mins read

Study: “Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial”
Publisher: Nature
Published date: February 2023
PubMed link to study: https://pubmed.ncbi.nlm.nih.gov/37118425/

The CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) phase 2 clinical trial indicates that long-term caloric restriction in healthy adults can slow the biological aging process. The study showed that participants who reduced their calorie intake by approximately 25% over two years experienced a modest but measurable decrease in the pace of aging, as assessed by DNA methylation biomarkers. These findings suggest that caloric restriction could be a potential strategy for improving longevity.

Feel welcome to share your own thoughts on this research in the comment section below as well. I will be happy to discuss and learn more about how you see its potential in this field.

The Impact of Long-term Caloric Restriction on Aging

Caloric restriction, defined as reducing calorie intake without depriving the body of essential nutrients. Numerous studies in animals have shown that caloric restriction can extend lifespan and delay the onset of age-related diseases. The CALERIE trial, a randomized controlled study, sought to investigate whether these benefits could also apply to humans.

The CALERIE Phase 2 Trial

The CALERIE trial involved 220 healthy adults who were not obese. Participants were randomly assigned to either a caloric restriction group, where they reduced their caloric intake by 25%, or a control group that continued to eat their usual diet. Over two years, researchers tracked changes in biological aging using advanced biomarkers derived from DNA methylation, which is a process that serves as a molecular indicator of aging.

You can view the official trial data on clinicaltrials.gov through this link: https://clinicaltrials.gov/study/NCT00427193

Key Findings: Slowing the Pace of Aging

One of the most significant outcomes of the CALERIE trial was the observation that long-term caloric restriction appeared to slow down the pace of biological aging. This was measured using the DunedinPACE algorithm, which estimates the rate at which aging-related changes accumulate over time. On average, participants in the caloric restriction group showed a reduction in the pace of aging by about 2-3% compared to the control group.

The authors noted a significant variability in how participants responded to long-term caloric restriction, with some experiencing larger reductions in the pace of aging than others. This suggests that individual differences, possibly related to genetics or adherence to the caloric restriction regimen, play a role in the effectiveness of long-term caloric restriction.

It is important to note that the study did not find significant changes in overall biological age as measured by other DNA methylation clocks (PhenoAge and GrimAge), and as such did not lead to significant changes in biological age.

Implications for Healthspan

The primary takeaway from the CALERIE trial is that caloric restriction may contribute to a slower pace of aging, which could potentially translate into a longer healthspan. Healthspan refers to the length of time an individual remains healthy, free from serious illness or disability. By slowing the rate at which aging-related damage accumulates, caloric restriction could help extend the period of life spent in good health.

However, it is important to note that the effects observed in the study were modest, and further research is needed to determine whether these changes in the pace of aging will lead to significant improvements in health outcomes such as reduced chronic disease incidence or increased lifespan.

Future Directions

The findings from the CALERIE trial provide a strong foundation for future research into long-term caloric restriction and other interventions aimed at slowing aging. Future studies with longer follow-up periods will be essential to understand the long-term benefits of caloric restriction fully. Additionally, research should explore how caloric restriction interacts with other factors, such as genetics and lifestyle, to influence aging.

The authors note the importance of longer-term follow-up studies to determine whether the observed changes in the pace of aging will translate into real-world benefits, such as reduced incidence of chronic diseases or increased lifespan.

Finally, there does not appear to be information about a Phase 3 clinical trial to follow up on the findings from the CALERIE trial. Hopefully, future studies will be able to validate these findings and build on them.

In Summary

The CALERIE trial demonstrates that long-term caloric restriction can modestly slow the pace of biological aging in healthy adults. While the effects are not dramatic, they suggest that long-term caloric restriction could potentially be a viable approach to extending healthspan. However, the authors emphasize that longer follow-up periods are needed to determine whether the observed slowing of biological aging translates into tangible benefits.

Read about more anti-aging research.

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Pursuit of Immortality

At Pursuit of Immortality I will keep you updated on the latest scientific research and technological breakthroughs in the field of anti-aging, and explore the question of whether it is possible to live forever.

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