Is Overnight Fasting before Surgery Too Much or Not Enough? How Basic Aging Research Can Guide Preoperative Nutritional Recommendations to Improve Surgical Outcomes: A Mini-Review

Abstract

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.

Fig. 1

Potential effects of DR on surgical stress resistance. a Model of the metabolic response to uncomplicated elective surgery vs. surgery in which complications such as MI, renal failure, or stroke occur. Also modeled is how DR affects metabolic rate prior to surgery as well as the metabolic response to surgical stress. b Cellular mechanisms of protection by dietary preconditioning. Dietary protein or essential amino acid restriction activates general control nonderepressible 2 (GCN2), AMP-activated protein kinase (AMPK), and sirtuin 1 (SIRT1) and represses mammalian target of rapamycin complex 1 (mTORC1) nutrient/energy sensing signal transduction pathways, resulting in increased hydrogen sulfide (H₂S) production by the transsulfuration pathway enzyme cystathionine γ-lyase (CGL) and improved insulin/insulin-like growth factor 1 (IGF-1) receptor sensitivity. H₂S can protect against acute stress via numerous mechanisms including direct antioxidant action, while improved insulin/IGF-1 sensitivity allow for increased prosurvival signaling, contributing to overall stress resistance. ATF4, activating transcription factor 4; FOXO, forkhead box O1; ROS, reactive oxygen species.