From the SENS Foundation: "To date, all successful interventions into the biological aging process in experimental animals have entailed modulation of basic metabolic pathways, generally through genetic or dietary manipulation. Of these, the earliest, most well-studied, and arguably the most robust, is Calorie restriction (CR): the reduction in dietary energy intake, without compromise of essential nutrients. With few exceptions, CR retards the biological rate of aging in nearly every species and strain of organisms in which it has been tested, ranging from rotifers, through small multicellular invertebrates, and most extensively to laboratory rodents; and although inconclusive, recent evidence also supports its effectiveness in dogs and nonhuman primates. Moreover, while necessarily preliminary, a growing body of human research has reported that rigorous CR, when practiced by previously normal-weight adults, results in physiological, functional, and perhaps even structural changes consistent with its translation to the human case. ... But despite the initial attractiveness of the notion; its strong theoretical basis; the high level of scientific interest that it has garnered; the launching of biotech startups originating in CR mimetic research; and the popularization and commercial exploitation of the concept by the dietary supplement industry - despite all of these drivers, the ensuing decade and a half or more of CR mimetic research have thus far been fruitless. Initially-promising compounds have failed to extend lifespan, while surprising findings have preempted the further investigation of what might otherwise have been novel targets for CR mimetics."