Reducing calories for two years did not change two widely used DNA-based aging clocks (PhenoAge and GrimAge), even though it did slow another aging marker called DunedinPACE, suggesting these tools measure different biological processes.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether DunedinPACE is uniquely responsive to caloric restriction compared to PhenoAge and GrimAge across all published human trials of dietary interventions.
A systematic review and meta-analysis of all RCTs and longitudinal studies that report changes in DunedinPACE, PhenoAge, and GrimAge in response to caloric restriction, intermittent fasting, or protein restriction, with standardized effect size comparisons.
Whether different dietary interventions (e.g., protein restriction vs. caloric restriction) differentially affect DunedinPACE versus PhenoAge/GrimAge.
A 3-arm RCT of 300 healthy adults aged 40–60 randomized to 20% caloric restriction, 20% protein restriction, or control for 24 months, measuring DunedinPACE, PhenoAge, and GrimAge at baseline, 12, and 24 months as primary outcomes.
Whether DunedinPACE, PhenoAge, and GrimAge predict distinct health outcomes over time, supporting their biological divergence.
A prospective cohort study of 10,000 adults aged 35–65 with serial DunedinPACE, PhenoAge, and GrimAge measurements over 15 years, analyzing which clock best predicts incident cardiovascular disease, neurodegeneration, or functional decline.
Whether individuals with accelerated DunedinPACE but normal PhenoAge/GrimAge have distinct clinical profiles compared to those with elevated PhenoAge/GrimAge but normal DunedinPACE.
A nested case-control study comparing 200 individuals with high DunedinPACE but low PhenoAge/GrimAge to 200 with low DunedinPACE but high PhenoAge/GrimAge, matched for age and sex, assessing clinical phenotypes and biomarkers.
Whether DunedinPACE, PhenoAge, and GrimAge show different correlations with physiological measures like grip strength, lung function, or metabolic rate in the same individuals.
A cross-sectional analysis of 1,500 adults aged 40–70 measuring all three DNAm clocks alongside 15 physiological markers of organ function, metabolism, and inflammation to compare correlation patterns.