Nutritional strategies to optimise cognitive function in the aging brain

Abstract

Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people.

Keywords: Aging; Cognition; Geometric framework; Intermittent fasting; Macronutrients.

Figure 1

Changes in the brain that occur in aging. Genetic changes, physical characteristics, cell-to-cell interactions, physiological changes, and cognitive differences are included. It has been suggested that these underlying physiological underpinning contribute to the symptoms of cognitive decline. AHP, afterhyperpolarization; EPSPs, excitatory postsynaptic potentials; LTP, long-term potentiation; PFC, prefrontal cortex.

Figure 2

A LPHC diet and its effect on the associated mTOR and related nutrient-sensing pathways. A hypothesis as to how a LPHC diet may affect brain physiology and neuronal function is included. A LPHC diet reduces mTOR activation and increases FGF21 activation, which in turn drives AMPK levels, contributing to the production of beneficial proteins PGC1α and SIRT1. In parallel, reduced IGF-1 levels heighten the sensitivity of IGF-1 receptors to IGF-1 and contribute to the production of AKT, which drives FOXO3 production, leading to improved insulin sensitivity (Ruderman et al., 2010; Willette et al., 2012; Cheng et al., 2012; Solon-Biet et al., 2015a).

Figure 3

A brief description of the contribution of individual macronutrients to brain health and cognitive function. Whilst the individual contributions have been relatively well-established, what remains is elusive is their proper ratios in order to maintain maximal brain fitness in late life.