Signaling pathways of dietary energy restriction and metabolism on brain physiology and in age-related neurodegenerative diseases.

Several laboratory animal models have shown that dietary energy restriction (ER) can promote longevity and improve various health aspects in old age. However, whether the entire spectrum of ER-induced short- and long-term physiological and metabolic adaptions is translatable to humans remains to be determined. In this review article, we present recent evidence towards the elucidation of the impact of ER on brain physiology and in age-related neurodegenerative diseases. We also discuss modulatory influences of ER on metabolism and overall on human health, limitations of current experimental designs as well as future perspectives for ER trials in humans. Finally, we summarize signaling pathways and processes known to be affected by both aging and ER with a special emphasis on the link between ER and cellular proteostasis.