Friend or Foe: Dietary Restriction and Its Protective Effects on Responses to Ionizing Radiation

Dietary restriction (DR) has been extensively investigated for its capacity to extend lifespan and mitigate age-associated pathologies. In the context of ionizing radiation (IR), DR-implemented through caloric reduction, selective nutrient restriction, or fasting-based regimens-has emerged as a significant modulator of both cellular and systemic responses to radiation exposure. Growing evidence suggests that DR influences radiation outcomes in a highly context-dependent manner, exerting either protective or sensitizing effects depending on tissue type, metabolic status, timing of intervention, and radiation conditions. This review synthesizes current knowledge regarding the mechanisms through which DR modulates responses to IR, with particular emphasis on oxidative stress regulation, inflammatory signaling, mitochondrial homeostasis, DNA damage responses, cellular quality-control pathways, and carcinogenic processes. We further discuss how distinct dietary paradigms interact with nutrient-sensing and stress-adaptive networks to influence radiation sensitivity and tissue recovery. Emerging evidence indicates that the timing, intensity, and composition of dietary interventions critically shape tissue responses to IR, underscoring the importance of considering nutritional status in radiation risk assessment and therapeutic planning. By integrating established findings with emerging mechanistic insights, this review highlights the translational potential of DR for improving outcomes in radiation oncology and reducing radiation-induced injury.