Table 1.

Studies included in the review and main results.

Studies included in the review
	Main results
Authors/Year
Martin et al., 2016	CR caused significant regional effects on the energy metabolism of the hippocampus, such as decreased activity of GSK3b and PGC1α.
Mahmoud A. Alomari et al., 2016.	CR associated with voluntary and forced exercise increases BDNF and memory. CR alone did not change BDNF levels.
Dong et al., 2016	CR increased learning and memory capacity, decreased GFAP, mTOR, S6K levels, and raised the expression of LC3B.
Burger et al., 2010.	CR led to the extension of the life span in Drosophila, but the decline in aversive learning performance associated with aging has not slowed.
Rich et al., 2010.	CR decreased cortical lesion size after traumatic brain injury, increased spatial memory, and BDNF expression.
Rumani Singh et al., 2015.	Intermittent fasting CR improved motor coordination, learning, decreased oxidative damage of proteins, recovery in the expression of energy regulating neuropeptides. Moreover, CR decreased the levels of nuclear factor kappa, cytochrome c, and positively regulated the expression of synaptophysin.
Villain et al., 2016.	Animals submitted to CR showed lower learning performance after restraint but maintained their locomotor abilities.
Navarro-Cruz et al., 2017.	Chronic resveratrol administration maintained the cytoarchitecture of the CA1 and CA2 regions of the rat hippocampus and improved cognitive performance.
Fu et al., 2017.	Mice submitted to chronic CR had impaired spatial recognition memory. Acute CR had positive and negative effects on memory.
Rühlmann et al., 2016.	CR had increased levels of plasma and brain FGF-21, increased level of brain phospho- FGFR1c, ERK1/2 and AMPK, decreased brain levels of mTOR, and phosphor-tau, increased synaptic plasticity and improved cognitive performance.
Parikh et al., 2016.	CR had neurovascular improvement, which has been shown to play an important role in vascular, cognitive, and mental health.
Kim et al., 2016	CR increased insulin sensitivity, decreased blood-brain barrier loss and glial activation induced by a high-fat diet and improved memory, reversed neurogranin expression induced by a high-fat diet and activation of Ca-dependent protein kinase II (2 +) / calmodulin and calpain.
Sarker et al., 2015.	CR and curcumin improved cognitive flexibility, suggesting a positive effect on frontal cortical functions.
Chen et al., 2015.	DNJ alleviated age-related disturbances such as declined sensorimotor capacity, anxiety, spatial and non-spatial memory, decreased serum insulin level; increased levels of insulin-like growth factor 1 receptor, synaptotagmin-1 presynaptic protein and astrocyte activation; decreased levels of insulin receptor, neurotrophic factor derived from the brain, pre-synaptic protein syntaxin-1 and acetylation of histones H4 in lysine 8 in the dorsal hippocampus.
Kaptan et al., 2015.	Low-calorie diet in adult female rats improved learning and spatial memory, increased proliferative cells and number of neurons in the hippocampal dentate gyrus and BDNF in the hippocampus and prefrontal cortex.
Kishi et al., 2015.	CR decreased insulin, systolic blood pressure, fasting blood glucose, adiponectin and oxidative stress in the hippocampus, increased BDNF in the hippocampus, and improved cognitive performance in model mice of metabolic syndrome.
Schleich et al., 2015.	Immunologically challenged animals had their spatial learning capabilities affected, increasing errors, and the time required to reach the goal of a complex maze. There was no effect of CR or interaction between factors.
Brownlow et al., 2014.	CR caused improvement in learning and short-term memory. Motor performance, spatial memory and total or phospho-tau levels were not affected by the intervention.
Yang et al., 2014.	CR decreased hippocampal BDNF levels, mTOR signaling, PI3K expression and Akt phosphorylation, delayed the decline in age-related autophagy and prevented the increase in poly-ubiquitinated proteins with aging.
Kuhla et al., 2013.	Lifelong CR exacerbated spontaneous locomotor activity and anxiety in mice, but improved cognitive performance resulting in an improvement in spatial memory.
Grayson et al., 2014.	Weight loss after CR, were associated with improvements in metabolic health and hippocampal-dependent learning. Rats treated with VSG exhibited deficit in spatial learning tasks in the Morris water maze. VSG animals showed high hippocampal inflammation comparable to that of obese controls. The RYGB and calorie-restricted controls exhibited an improvement in inflammation. Ghrelin treatment did not alleviate the inflammation of the hippocampus.
Gräff et al., 2013.	CR retarded neurodegeneration and synaptic dysfunction, increased the expression of SIRT1 protein regulating life expectancy.
Dhurandhar et al., 2013.	Long-term administration of ghrelin agonist improved performance in the water maze, reduced amyloid beta (Aβ) and inflammation (microglial activation) in a similar manner to CR.
Kishi and Sunagawa, 2012.	Physical training avoided the cognitive decline, which was evaluated by the Morris water maze test. Physical training associated with CR caused greater protection against cognitive decline than just physical training or CR.
Porquet et al., 2013.	Resveratrol supplements increased life expectancy. Resveratrol reduced cognitive impairment and plays a neuroprotective role, reducing amyloid load and reducing tau hyperphosphorylation.
Lee et al., 2012.	The facilitation of NQO1 activity by feeding β-lapachone (βL), prevented the age-related decline in motor and cognitive function in elderly mice.
Rodriguez et al., 2012.	Maternal CR in baboons caused improvement in the learning of female puppies and impaired learning in male puppies, which also showed increased impulsivity.
Rumani Singh et al., 2012.	In rats, Intermittent fasting improved motor coordination and cognitive abilities, decreased oxidative damage and improved IV activity of the mitochondrial complex.
Dal-Pan et al., 2011.	Both CR and resveratrol supplementation (RSV) increased spontaneous locomotor activity and improved working memory in the spontaneous alternation task. RSV supplementation increased the performance of spatial memory in the circular platform task, but not the CR.
Steinman et al., 2011.	In females, CR can cause differential effects on acquisition and learning, depending on the photoperiod.
Chouliaras et al., 2011.	The age-related increase in DNA methyltransferase 3a (Dnmt3a) -IR in CA3 and CA1−2 cells in type I cells was mitigated by CR, but not by overexpression of SOD. The density of Dnmt3a type II immunoreactive cells decreased with age, without significant effects of CR and SOD.
McEwen and Paterson, 2010.	30 % CR administered from global ischemia did not decrease brain damage or improve long-term recovery.
Liu et al., 2017.	Short-term CR after mTBI improved mTBI-induced cognitive dysfunction, increased autophagy, and suppressed astrocyte activation.
Jeon et al., 2016.	CR reduced fatty liver and insulin resistance in diabetic mice induced by obesity (ob / ob), increased levels of O-linked N-acetylglucosamine in the hippocampus (O-GlcNAc) and GlcNAc transferase and decreased protein expression calcium / calmodulin-dependent kinase II, lipocalin-2 and phosphorylated tau. CR reduced the learning deficits normally seen in ob/ob mice.
Delic et al., 2015.	CR was not able to restore the decrease in the activity of complex I, respiratory rate stimulated by ADP and the increase in the potential of the mitochondrial membrane that occurs in the mitochondria of mice that express human P301 l (Tg4510). CR led to a genotype-independent reduction in F0F1-ATPase mitochondrial activity.
Akitake et al., 2015.	Moderate maternal RC induced intrauterine growth retardation (IUGR). Offspring had low birth weight and a delay in the development of physical and coordinated movements. IUGR's children exhibited mental deficiencies.
Babenko and Shakhova, 2014.	The sensitive redox-neutral SMase was important in interrupting the renewal of sphingolmyelin (SM) in the hippocampus and neocortex in old age, and CR prevented accumulation of age-dependent ceramide through the neutral targeting of the SMase.
Wei et al., 2014.	The rats in the d-gal group exhibited deficits in spatial reference memory in the Morris water maze test, while the rats in the d-gal group submitted to CR exhibited almost normal cognitive function, indicating that the CR protects the learning and memory of the harmful effects induced by d-gal.
Park et al., 2013.	CR increased cell divisions in the dentate gyrus of female mice, suggesting that CR increases the number of divisions by which neural and progenitor stem cells suffer in the aging brain.
Jin et al., 2016.	Metformin rescued cells from mutant hunting-induced toxicity (HTT) and maintained levels of ATP in cells expressing mutant HTT and prevented depolarization of the mitochondrial membrane and excess fission and modulated the disturbed mitochondrial dynamics in DH cells.