Neurotrophic effects of intermittent fasting, calorie restriction and exercise: a review and annotated bibliography

Abstract

In the last decades, important progress has been achieved in the understanding of the neurotrophic effects of intermittent fasting (IF), calorie restriction (CR) and exercise. Improved neuroprotection, synaptic plasticity and adult neurogenesis (NSPAN) are essential examples of these neurotrophic effects. The importance in this respect of the metabolic switch from glucose to ketone bodies as cellular fuel has been highlighted. More recently, calorie restriction mimetics (CRMs; resveratrol and other polyphenols in particular) have been investigated thoroughly in relation to NSPAN. In the narrative review sections of this manuscript, recent findings on these essential functions are synthesized and the most important molecules involved are presented. The most researched signaling pathways (PI3K, Akt, mTOR, AMPK, GSK3β, ULK, MAPK, PGC-1α, NF-κB, sirtuins, Notch, Sonic hedgehog and Wnt) and processes (e.g., anti-inflammation, autophagy, apoptosis) that support or thwart neuroprotection, synaptic plasticity and neurogenesis are then briefly presented. This provides an accessible entry point to the literature. In the annotated bibliography section of this contribution, brief summaries are provided of about 30 literature reviews relating to the neurotrophic effects of interest in relation to IF, CR, CRMs and exercise. Most of the selected reviews address these essential functions from the perspective of healthier aging (sometimes discussing epigenetic factors) and the reduction of the risk for neurodegenerative diseases (Alzheimer’s disease, Huntington’s disease, Parkinson’s disease) and depression or the improvement of cognitive function.

Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review

“…Higher BDNF concentrations in the hippocampus have been associated with both improved cognitive function [48] and metabolic health [49]. Recently, many animal (rodent) studies have revealed that IF positively stimulates the production of BDNF in the hippocampus, cerebral cortex, and striatum and reduces cognitive deficits by enhancing neurotrophic support and suppressing the expression of pro-inflammatory cytokines [18,50,51].…”

Changes of Signaling Pathways in Hypothalamic Neurons with Aging

“…The geroprotective effect of SIRT1 is regulated via p53, NF-κB, mTOR, PGC1α, and FOXO signal pathways [169][170][171]. Sirtuins are also required for caloric restriction-induced life span extension [171,172].…”