Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection as well as overlapping metabolic consequences has not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H₂S)-dependent cysteine catabolism as a potential common mechanism of organ protection. Importantly, these metabolic changes can be recapitulated in patients preconditioned by a diet limiting sulfur-containing amino acids indicating conserved diet-induced mechanisms of stress-resistance that may ultimately lead to clinical application.

中文翻译：

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饮食诱导的肾保护作用的系统分析揭示了半胱氨酸分解代谢的重叠和保守变化

热量限制 (CR) 可延长寿命并增强从酵母到灵长类动物的细胞抗压性，使 CR 成为临床器官保护的有吸引力的策略。由于体弱患者的依从性、可行性和安全问题，将 CR 转化为患者是复杂的。新颖的定制饮食方案，调节宏量和微量营养素的饮食组成，而不是减少卡路里摄入量，有望提供类似的保护作用和增加的可转化性。然而，尚未进行直接的头对头比较，以确定最有效的器官保护方法以及重叠的代谢后果。我们系统地分析了六种饮食预处理方案——禁食模拟饮食 (FMD)、生酮饮食 (KD)、支链氨基酸饮食限制 (BCAA)、限制含硫氨基酸 (SR80/100) 和 CR 的两种饮食方案 - 在肾脏缺血再灌注损伤 (IRI) 的啮齿动物模型中量化饮食诱导的肾脏弹性。在给予的饮食中，FMD、SR80/100 和 CR 可有效防止 IRI 后的肾脏损伤。有趣的是，这些方法显示氧化和硫化氢（H₂ S) 依赖性半胱氨酸分解代谢作为器官保护的潜在常见机制。重要的是，这些代谢变化可以在通过限制含硫氨基酸的饮食预处理的患者中重现，表明保守的饮食诱导的抗压机制可能最终导致临床应用。