NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging

Abstract

Current sociodemographic predictions point to a demographic shift in developed and developing countries that will result in an unprecedented increase of the elderly population. This will be accompanied by an increase in age-related conditions that will strongly impair human health and quality of life. For this reason, aging is a major concern worldwide. Healthy aging depends on a combination of individual genetic factors and external environmental factors. Diet has been proved to be a powerful tool to modulate aging and caloric restriction has emerged as a valuable intervention in this regard. However, many questions about how a controlled caloric restriction intervention affects aging-related processes are still unanswered. Nutrient sensing pathways become deregulated with age and lose effectiveness with age. These pathways are a link between diet and aging. Thus, fully understanding this link is a mandatory step before bringing caloric restriction into practice. MicroRNAs have emerged as important regulators of cellular functions and can be modified by diet. Some microRNAs target genes encoding proteins and enzymes belonging to the nutrient sensing pathways and, therefore, may play key roles in the modulation of the aging process. In this review, we aimed to show the relationship between diet, nutrient sensing pathways and microRNAs in the context of aging.

Keywords: Mediterranean diet; caloric restriction; cardiovascular disease; circulating microRNAs; dietary restriction; healthy aging; intermittent fasting; lifespan; microRNAs; type 2 diabetes.

Figure 1

Caloric restriction (CR)-mediated modulation of nutrient sensing pathways. CR results in a decrease in plasma glucose levels that, in turn, decrease IGF-1 and insulin levels. As a result, the signaling downstream insulin receptor (IR) and IGF-1R decreases. In this situation, AKT is in its un-phosphorylated inactive form and, thus, mTOR is also inactive. The decrease in the cellular availability of glucose also increases AMP/ATP ratio and, consequently, AMPK is activated. AMPK also inhibits mTOR complex 1 and increases NAD⁺/NADH ratio. SIRT1 is a histone deacetylase activated by NAD⁺. Coordinately, these interconnected nutrient-sensing pathways modulate cell homeostasis, cellular function, senescence, autophagy and metabolism, contributing to healthy aging and longer lifespan. Images from Servier Medical Art have been included in this figure (Available online: http://www.servier.com/Powerpoint-image-bank).