Calorie Restriction Modulates Four Hallmarks of Aging in Prediabetic Adults: A Proteomics PREVIEW Sub-Study

Prediabetes, a metabolic condition marked by impaired fasting glucose and/or glucose tolerance, is associated with multi-organ damage, heightened mortality risk, and accelerated aging, even prior to the onset of diabetes. Calorie restriction (CR) without depriving essential nutrients is one of the most effective dietary interventions for improving metabolic health and halting the progression to type 2 diabetes. However, how CR modulates aging-related processes, particularly at the systemic proteome level, remains incompletely understood in individuals at risk of diabetes. In this study, we employed targeted and untargeted proteomic approaches to evaluate the impact of an 8-week, 40-50% energy-restricted diet in 44 prediabetic adults from Sydney, Australia, enrolled in the PREVIEW study. Informed consent was obtained from all participants, who achieved ≥12% body weight loss during the intervention. Longitudinal changes in 2,059 circulating proteins were analyzed to investigate the systemic effects of CR on aging-related pathways.