The Effect of Calorie Restriction on Biological Aging
Summary ID02-HA-RS-00042
Research Summary
Original Publication
Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
Journal
Nature Aging, .
- Category
- 02Healthy Aging
- Evidence
- Randomized controlled trial
- Summary Type
- Core
What Was Studied?
Calorie restriction has been shown to extend healthy lifespan in several experimental species. Whether it can influence biological aging in humans is much less certain.
The CALERIE trial investigated this question in healthy adults without obesity.
The original trial included 220 adults. Participants were randomly assigned to either calorie restriction or a control group for two years. The intervention aimed to reduce calorie intake by 25%.
In practice, participants achieved an average calorie reduction of approximately 11.9%.
For this analysis, researchers examined blood samples from 197 participants with available DNA methylation data. This included 128 participants in the calorie-restriction group and 69 controls.
The researchers compared several epigenetic measures of aging. These included PhenoAge, GrimAge and DunedinPACE.
These measures do not assess exactly the same aspect of aging. PhenoAge and GrimAge estimate accumulated biological age. DunedinPACE estimates how quickly biological aging is occurring.
This distinction became central to the findings.
Key Findings
1. Calorie restriction slowed the measured pace of biological aging.
The clearest effect was seen with DunedinPACE.
Compared with the control group, DunedinPACE decreased in the calorie-restriction group after 12 months. The effect remained after 24 months.
The difference corresponded to approximately a 2–3% reduction in the measured pace of aging.
2. Other measures of biological age did not significantly change.
Calorie restriction did not significantly change biological age measured by PhenoAge or GrimAge.
This is an important distinction.
The intervention did not make participants measurably “biologically younger” according to these clocks. Instead, it affected a measure designed to capture how rapidly aging-related biological changes are occurring.
3. Greater calorie restriction was associated with a larger DunedinPACE effect.
Most participants did not achieve the prescribed 25% calorie reduction.
The average reduction was approximately 11.9%.
Participants who achieved at least 10% calorie restriction showed larger reductions in DunedinPACE than those who achieved less than 10%.
This suggests a possible dose-response relationship. However, these analyses were secondary and do not establish an optimal level of calorie restriction.
4. The effect was small and individual responses varied.
The researchers described the overall treatment effect as small.
There was also substantial overlap between the calorie-restriction and control groups. Some participants showed considerably larger changes than others.
The findings therefore support a biological effect at the group level. They do not mean that every individual will respond in the same way.
Why It Matters for Longevity
Calorie restriction is one of the most extensively studied nutritional interventions in longevity research.
In animal models, it can influence multiple biological pathways associated with aging. It can also extend healthy lifespan.
CALERIE provides important human evidence.
It suggests that the pace of biological aging may be modifiable through nutrition.
This is particularly relevant because the participants were healthy adults without obesity. The study was therefore not simply testing calorie restriction as a treatment for obesity.
It was examining whether a nutritional intervention could influence biological processes associated with aging itself.
However, an important distinction remains.
A change in a biomarker of aging is not the same as demonstrating a longer life.
The study lasted two years. It did not establish whether the observed DunedinPACE change leads to fewer chronic diseases, longer healthspan or increased lifespan.
Long-term follow-up is needed to answer these questions.
Clinical Perspective
The CALERIE findings support the concept that moderate, sustained calorie restriction without malnutrition may influence biological processes associated with aging.
They do not show that greater calorie restriction is always better.
The intervention was intensive. Participants received substantial dietary and behavioral support. This differs from simply advising someone to eat less.
Nutritional quality also remains essential. Adequate protein, micronutrients and preservation of lean body mass are particularly important when reducing energy intake.
The study also highlights an important issue in biological age testing.
Different biomarkers measure different aspects of aging. DunedinPACE changed with the intervention. PhenoAge and GrimAge did not.
A single biological age result should therefore not be interpreted as a complete measure of how an individual is aging.
Key Takeaway
Two years of calorie restriction slowed a measure of the pace of biological aging by approximately 2–3%. Other measures of biological age did not significantly change. Whether this translates into longer healthspan or lifespan remains unknown.
Reviewed and Summarized by
Source Publication
- Title:
- Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
- Authors:
- Waziry R, Ryan CP, Corcoran DL, et al.
- Journal:
- Nature Aging, February 2023.




