Two-year caloric restriction attenuated biological age increases across multiple organ systems in a randomized trial

This Phase 2 randomized controlled trial enrolled a subset of 185 participants. The population included 120 individuals in the caloric restriction group and 65 in the ad libitum diet group. All participants had available organ-specific biomarkers at baseline and at least one follow-up assessment at 12 or 24 months. The setting location was not reported. The study design allowed for the evaluation of sustained caloric restriction over a two-year period.

The intervention consisted of two years of sustained caloric restriction. The comparator was an ad libitum diet. The primary outcome measured longitudinal changes in organ-specific biological age across multiple physiological systems. Secondary outcomes included cardiovascular biological age, immune biological age, kidney biological age, liver biological age, metabolic biological age, and whole body biological age.

Results for the metabolic system biological age showed that caloric restriction mitigated organ-specific increases in biological age relative to the ad libitum diet. The effect size was -0.54 years at 12 months and -0.63 years at 24 months. The p-value was 1.26 x 10^-4 at 12 months and 3.02 x 10^-4 at 24 months. For the cardiovascular system biological age, the effect size was -0.82 years at 12 months and -1.00 years at 24 months. The corresponding p-values were 9.55 x 10^-4 at 12 months and 1.96 x 10^-4 at 24 months.

The whole body biological age demonstrated an effect size of -1.00 years at 12 months and -1.27 years at 24 months. The p-values were 2.53 x 10^-4 at 12 months and 1.20 x 10^-4 at 24 months. The immune system biological age showed an effect size of -0.65 years at 12 months and -0.62 years at 24 months. The p-values were 1.83 x 10^-4 at 12 months and 2.92 x 10^-4 at 24 months. For the liver biological age, the increase was modestly slowed only at 24 months with an effect size of -0.54 years and a p-value of 8.30 x 10^-4.

Kidney biological age remained unaffected with no effect reported. Metabolic and whole body age showed more pronounced attenuation of increases associated with a higher dose of caloric restriction greater than or equal to 12.4%. Significant declines in multiple biological ages were associated with achieving the 20% caloric restriction target. Absolute numbers were not reported for these outcomes.

Safety and tolerability findings were not reported. Serious adverse events were not reported. Discontinuations were not reported. Adverse events were not reported. These findings support organ-specific biological ages as sensitive surrogate endpoints for detecting early responses to anti-aging interventions and as practical tools for monitoring or targeting organ-specific aging in future efforts. The study was a randomized controlled trial. Questions remain regarding long-term sustainability and broader applicability beyond this specific subset.