Longchamp Alban, Harputlugil Eylul, Corpataux Jean-Marc, Ozaki C Keith, Mitchell James R
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Gerontology. 2017;63(3):228-237. doi: 10.1159/000453109. Epub 2017 Jan 5.
Dietary restriction (DR) is best known for extending lifespan in experimental model organisms, but also increases resistance to a variety of clinically relevant stressors, including those associated with surgery. Extended periods of DR, lasting months to years, are required for optimal longevity benefits in rodents, but short-term dietary preconditioning (less than 1 week) remarkably protects from acute injury. Here, we discuss recent advances in our understanding of the mechanistic basis of short-term DR and fasting in the context of surgical stress resistance, including upstream amino acid sensing by the GCN2 and mTORC1 pathways, and downstream effector mechanisms including increased insulin-dependent prosurvival signaling and elevated endogenous hydrogen sulfide production. We also review the current trend in preoperative nutrition away from preoperative fasting and towards carbohydrate loading. Finally, we discuss the rationale for the nonmutually exclusive use of brief DR or pharmacological DR mimetics to precondition against the stress and potential complications of surgery.
饮食限制(DR)以延长实验模式生物的寿命而闻名,但它也能增强对多种临床相关应激源的抵抗力,包括与手术相关的应激源。在啮齿动物中,要获得最佳的长寿益处需要持续数月至数年的长期饮食限制,但短期饮食预处理(少于1周)能显著保护机体免受急性损伤。在此,我们讨论了在手术应激抵抗背景下,我们对短期饮食限制和禁食的机制基础的最新理解进展,包括GCN2和mTORC1途径对上游氨基酸的感知,以及下游效应机制,如胰岛素依赖性促生存信号增加和内源性硫化氢产生升高。我们还回顾了术前营养从术前禁食转向碳水化合物负荷的当前趋势。最后,我们讨论了非排他性地使用短期饮食限制或药理学饮食限制模拟物来预处理手术应激和潜在并发症的基本原理。