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Solid Plate-based Dietary Restriction in Caenorhabditis elegans
Published on: May 28, 2011
Effect of caloric restriction on organ-specific biological aging in a randomized clinical trial
Yucan Li1, Xinming Xu2, Raghav Sehgal3
1State Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 201203, China; Department of Biostatistics, School of Public Health, The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, 200032, China.
Background And Aims:
Caloric restriction (CR) has demonstrated benefits in improving individual biomarkers and longevity, but its organ-specific systemic effects remain unclear. We aimed to quantify the effects of long-term CR on longitudinal changes in organ-specific biological age across multiple physiological systems.
Methods:
In the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 randomized controlled trial, a subset of 185 participants (120 CR, 65 ad libitum) with available organ-specific biomarkers at baseline and at least one follow-up assessment at 12 or 24 months was analyzed. Participants were assigned to 2 years of sustained CR or an ad libitum diet. Five organ-specific biological ages (cardiovascular, immune, kidney, liver, metabolic) and the whole body age were assessed at both time points. Intention-to-treat, dose-response, and treatment-on-the-treated analyses were performed to evaluate changes in these biological age measures over time.
Results:
CR mitigated organ-specific increases in biological age relative to the ad libitum diet, with the most robust effects in metabolic system (-0.54 years at 12 months, P = 1.26 × 10-5; -0.63 years at 24 months, P = 3.02 × 10-7) and cardiovascular system (-0.82, P = 9.55 × 10-5; -1.00, P = 1.96 × 10-6), followed by whole body (-1.00, P = 2.53 × 10-3; -1.27, P = 1.20 × 10-4) and immune system (-0.65, P = 1.83 × 10-3; -0.62, P = 2.92 × 10-3); liver age increase was modestly slowed only at 24 months (-0.54, P = 8.30 × 10-3), while kidney age remained unaffected. Participants with a higher dose of CR (≥12.4%) showed a more pronounced attenuation of increases in metabolic and whole body age. Adherence analysis further showed that achieving the 20% CR target led to significant declines in multiple biological ages.
Conclusion:
CR exerts heterogeneous effects on biological aging across organ systems, with the most pronounced responses in metabolic, cardiovascular, immune, and whole body systems. 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.
Clinical Trial Registration:
ClinicalTrials.gov identifier NCT00427193 (registered January 25, 2007; URL: https://clinicaltrials.gov/study/NCT00427193).
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