Intermittent and periodic fasting trigger metabolic reprogramming and enhance cellular repair and antioxidant defenseFasting methods may improve metabolism and cellular repair

Intermittent fasting (IF) and Periodic fasting (PF) are biologically plausible non-pharmacological interventions. They trigger core metabolic reprogramming from glucose catabolism to ketogenesis and activate conserved nutrient-sensing networks including AMPK and sirtuins, coupled with mTOR/IGF-1 axis suppression. Such adaptive regulation enhances cellular repair, antioxidant defense and inflammatory homeostasis, conferring multi-system benefits encompassing metabolic improvement, neuroprotection, anti-tumor activity and healthspan extension. Clinically, time-restricted eating (TRE) and fasting-mimicking diets (FMDs) have demonstrated feasibility and short-term efficacy in pilot clinical studies, although their long-term translational potential and durability of benefits remain unproven. However, current research faces major bottlenecks: over-reliance on homogeneous animal models, insufficient high-quality long-term human trials, unresolved individual response heterogeneity, and the lack of validated non-invasive biomarkers and systematic long-term safety evidence. This mini-review systematically elaborates the core regulatory mechanisms of IF and PF through a hierarchical framework that distinguishes primary drivers from secondary consequences and speculative mechanisms, critically evaluates the evidence base across model systems, analyzes key translational barriers, and proposes a prioritized research agenda. Our objective is to provide a conceptually grounded synthesis that identifies genuine scientific uncertainty, distinguishes established knowledge from speculation, and offers a perspective capable of guiding future investigation toward precise clinical translation.