Impact of caloric restriction on biological aging: insights from a composite biomarker index in older adults

Caloric restriction (CR) extends lifespan and delays age-related diseases in model organisms, yet its effects on biological aging in humans remain unclear. We pooled data from seven randomized CR trials (n = 829) and examined randomization to CR and change in weight with a biomarker index composed of CRP, IL-6, cystatin C, insulin, GDF-15, and TNF-R1. CR improved the composite biomarker index. The effect of CR decreased from -2.2 to -1.2 (95% CI -2.0 to -0.3) after adjustment for weight, while the effect of weight loss decreased from 0.22 to 0.16 (95% CI 0.09 to 0.23) when CR was included in the model, suggesting improvements in the biomarker index are only partially mediated by the amount of weight loss. Mediation analyses showed that only 48.5% (95% CI 22.6 to 82.2%) of the CR effects were explained by weight loss. These findings support the potential for composite biomarker indices as measures of intervention response and CR as a strategy to target biological aging.