To eat or not to eat - anti-ageing effects of energy restriction

This chapter is focused on the most efficient and best-researched way to increase longevity and reduce the incidence of age-associated diseases in animals - energy restriction. In the first part of the chapter, the various protocols employed in energy-restricted animals, including those that restrict a specific nutrient, such as proteins or methionine, are presented and compared. The main results concerning animal experiments, including recent trials in nonhuman primates as well as controlled studies (CALERIE) and observational studies in humans subjected to long-term voluntary energy restriction, are also reviewed and discussed. Further, a detailed analysis is performed of the known effects of energy restriction on whole organisms, considering longevity and the incidence of age-associated diseases such as cancer and autoimmune diseases, body composition, metabolic features, immune system responses and inflammatory and neuroendocrine modulation. Growing evidence supports the hypothesis that energy restriction induces profound modifications in cellular metabolism. In this chapter we review the most recent literature concerning the molecular mechanisms associated with energy-restriction adaptation, such as the shift in gene expression, the activation of sirtuins, metabolic reprogramming and the control of oxidative stress and autophagy. Some energy restriction mimetics or nutrients that capture the positive health effects of energy restriction and the potential beneficial effects to human health are considered. In the second part of the chapter the effects of obesity, which, in contrast to energy restriction, seems to induce premature ageing, are presented. The role of adipose tissue on the endocrine milieu and metabolism is considered, as well as the molecular modulation of mitochondrial and endoplasmic reticulum functions by obesity. The effects of natural compounds extracted from plants on adipose tissue accretion and metabolism and their potential applications for obesity control in the elderly are also discussed. Lastly, the anti-obesity role of minerals, often insufficient in Western diets, particularly in the aged population, is considered.