Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy-d-glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.
Keywords: 2DG 2-deoxy-d-glucose; AMPK AMP-activated protein kinase; ER energy restriction; ERM energy restriction mimetic; FOXO forkhead box O; GH growth hormone; IGF-1 insulin-like growth factor 1; NIA United States National Institute on Aging; Nrf2 nuclear factor (erythroid-derived 2) like 2; PGC1α PPAR γ coactivator 1-α; ROS; RSV resveratrol; SIRT sirtuin; SOD superoxide dismutase; SPD spermidine; T2DM type 2 diabetes mellitus; UCP uncoupling protein; mTOR mammalian target of rapamycin; mTORC1 mammalian target of rapamycin complex 1; p-AMPK phosphorylated AMPK; reactive oxygen species; Energy restriction; Energy restriction mimetics; Healthy ageing; Lifespan; Longevity.