Caloric restriction

**Consensus** Caloric restriction(definition) (CR), implemented without causing malnutrition, successfully delays aging, extends lifespan, and delays disease onset across diverse species, including primates such as rhesus monkeys [4]. Mechanistically, CR is closely linked to redox metabolism and the mitigation of oxidative stress—a major postulated causal factor of senescence(definition) driven by reactive oxygen metabolites [2]. Furthermore, the longevity and metabolic adaptations prompted by CR-like states are modulated by conserved endocrine and regulatory pathways, including insulin/insulin-like signaling (such as *daf-2* in *C. elegans*) [5] and sirtuin proteins (such as Sir2 homologs) [8], which can be pharmacologically targeted by sirtuin activators to mimic the anti-aging effects of CR [6].

**Open Questions** While the phenomenological benefits of CR are well-documented in model organisms and primates [4], open questions remain regarding the exact translation of CR and dietary interventions (such as time-restricted eating or specific amino acid restrictions) to human clinical relevance. Specifically, the degree to which real-life human dietary regimens achieve clinically significant metabolic benefits versus mild statistical changes requires further clarification [9], alongside a deeper understanding of how divergent redox-metabolism adaptations intersect with long-term aging outcomes [10].

**Strength of Evidence** The evidence base supporting the anti-aging and disease-delaying efficacy of caloric restriction(definition) ranges from robust phenomenological and longitudinal studies in diverse metazoans and primates [4] to well-established molecular frameworks involving oxidative stress [2], insulin signaling [5], and sirtuin regulation [8]. Evidence concerning specific dietary subsets or human translational interventions (like time-restricted eating) is more variable and currently yields nuanced clinical results [9].