Caloric restriction

**Consensus** Caloric restriction (CR), implemented without causing malnutrition, delays aging processes and extends lifespan across diverse species [4]. In primates, a 20-year longitudinal adult-onset study in rhesus monkeys demonstrates that CR successfully delays disease onset and reduces mortality [4]. Mechanistically, the anti-aging and metabolic benefits of CR are closely intertwined with reductions in oxidative stress and reactive oxygen metabolites [2], as well as the engagement of conserved regulatory pathways involving insulin/IGF-1 signaling (such as *daf-2* in *C. elegans*) [5] and sirtuin proteins (such as Sir2 homologues), which modulate longevity and can be pharmacologically mimicked by sirtuin activators [6, 8].

**Open Questions** While the phenomenological and preclinical impacts of CR are well-documented across model organisms and non-human primates, translating these findings into clinically relevant, real-world human interventions remains an active area of study. Specifically, variations in dietary modifications—such as comparing classic caloric restriction to time-restricted eating or specific amino acid restrictions (e.g., sulfur amino acid restriction)—exhibit divergent metabolic and redox adaptations [9, 10], and their long-term efficacy and feasibility in human populations require further clarification.