Less is more: Caloric regulation of neurogenesis and adult brain function

Abstract

Calorie intake is essential for regulating normal physiological processes and is fundamental to maintaining life. Indeed, both extremes of calorie intake result in increased morbidity and mortality. In this review, we discuss the effect of calorie intake on adult brain function, with an emphasis on the beneficial effects of mild calorie restriction.Recent findings relating to the regenerative and protective effects of the gastrointestinal hormone, ghrelin, suggest that it may underlie the beneficial effects of calorie restriction. We discuss the putative cellular mechanisms underlying the action of ghrelin and their possible role in supporting healthy brain ageing. K E Y W O R D Sacyl-ghrelin, adult hippocampal neurogenesis, calorie restriction, diet-induced obesity | INTRODUCTIONThe energy status of an organism is tightly controlled around a setpoint by hormonal and neural systems. These neuroendocrine checks and balances promote homeostasis, thereby ensuring an appropriate energy supply for the energetic demands of metabolism, physical activity, growth and repair.Disturbances to this homeostasis result in multiple physiological impairments, including age-related conditions such as type 2 dibetes mellitus and obesity. Perhaps less well recognised are the consequences of metabolic dysfunction on neuronal health and cognition.Diet-induced obesity (DIO) is a risk factor for neurodegenerative diseases such as Parkinson's disease (PD) and dementia. Conversely, calorie restriction (CR) (ie, an approximate 30% reduction in calorie intake) protects against neurodegeneration and promotes cognitive function (Figure 1). Indeed, there is a growing body of work supporting the CR paradigm as a tool for promoting lifespan and, perhaps more importantly, healthspan.1 However, the physiological mechanisms underlying these effects are not fully understood. Here, we review literature that identifies calorie intake as an important regulator of nerve cell function, with important implications for neurodegenerative disorders. Moreover, we describe recent research showing that CR promotes new neurone formation (neurogenesis) and neuroprotection in the adult brain and discuss the possible mechanisms that underpin this effect. | CALORIE RESTRICTION REGULATES BRAIN FUNCTIONCalorie restriction, in the absence of malnutrition, has beneficial effects on brain function, including reducing the incidence of age-related neurodegenerative disease, 2 eliciting anti-depressant behaviour 3 and improving memory function in rodents. 4 In nonhuman primates, prolonged CR in adulthood decreases the incidence of age-related disease, including measures of brain atrophy and glucose regulation. 5-7Translation of the carefully controlled CR experiments from preclinical models to humans is problematic. In particular, it is difficult to re-capitulate experimental controls such as genetic background and home environment (diet, temperature and lighting) that are standard in biomedical laboratory research. Nonetheless, in adult humans, a 3-month period of CR impr...

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“…Several good recent reviews are available, discussing the neurocognitive effects of bariatric surgery 150,151 and caloric restriction. 152,153 Our team also published a paper in 2015 discussing the benefits and drawbacks of surgical versus nonsurgical interventions for obesity and their potential effects on cognitive function. 154 The conclusions from that literature are similar to conclusions already discussed: decisions about what intervention to recommend need to be individually tailored, based on individual health and personality characteristics.…”

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