Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

Abstract

The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferatoractivated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…It is possible that the association between increased risk of developing AD and excess body weight reflects the potential effect of a diet high in simple sugars and fats to the development of AD. A recent study showed reducing caloric intake increases healthspan, reduces damage in the brain due to aging, and provides greater maintenance of various brain functions (Martin et al, 2008; Martin, Golden, Egan, Mattson, & Maudsley, 2007; Martin, Ji, Maudsley, & Mattson, 2010; Martin, Mattson, & Maudsley, 2006). …”

Ageing and the brain

“…It has been known for many decades that restricting daily calorie intake in rodents and some other animals increases longevity substantially [85,86]. It is speculated that this may be because in times of famine reproductive activity is reduced, since any offspring would be unlikely to survive.…”

Caloric restriction: Impact upon pituitary function and reproduction

“…In addition to these humoral factors connecting energy balance to reproduction, it has recently been posited that there is a specific glucose-sensing mechanism in the CNS itself that is mediated via noradrenergic stimulation of the nuclei of the solitary tract (NTS: Kinoshita et al, 2003). Profound nutritional signals such as those imposed by CR or IF exert a wide range of physiological effects across the whole organism subjected to the dietary change (for review see Martin et al, 2006). One of the most profound alterations that take place with these dietary regimes is disruption of the complex neuroendocrine feedback axes centered around the anterior pituitary.…”

“…In experimental paradigms in various species, it has been shown that specific alterations in available dietary energy, e.g. mild caloric restriction (CR) or intermittent fasting (IF), can have beneficial and long-lasting effects on animal physiology (for review, see Martin et al, 2006). Low, moderate and high levels of dietary energy intake can affect reproductive function in different ways.…”