Caloric restriction (CR) is a general strategy for improving wellbeing and lifespan. It is more than a simple limitation of calories for maintenance of body weight; CR is the dramatic reduction of caloric intake to levels that may be significantly (up to 50% in some cases) below that for maximum growth and fertility, but nutritionally sufficient for maintaining overall health (“undernutrition without malnutrition”).1 It remains one of the most researched and successful approaches to life extension in laboratory settings. Although the effects of CR on health are diverse, its mechanisms are not fully understood, and are thought to involve the activation of survival mechanisms that have been evolutionarily conserved to protect organisms from stress.
The idea of extending healthspan (the period of healthy living before the onset of age-related disease) and lifespan by lowering food intake is not a new one. Louis Caranaro’s 16th century best-selling anti-aging book suggested that longevity would come to those who ate only enough to sustain life; Benjamin Franklin supported the concept of abstinence as a defense against disease two centuries later.2 But it was the work of McCay in the 1930’s that first demonstrated that reducing calories below the level required for maximum fertility, while avoiding malnutrition, could extend the mean and maximum lifespan of laboratory rats by 40% or more.3 In the years following that seminal work, the health and longevity effects of CR have been observed in a wide range of organisms, ranging from single-celled Saccharomyces, to primates and man.
The practical challenge of long-term or lifetime CR has recently generated interest in caloric restriction mimetics (CRMs), an alternative to CR which may provide the pro-longevity benefits without an actual reduction in caloric intake.4 CRMs are a broad class of compounds and interventions that may promote life- and health-span by a diversity of mechanisms, ranging from induction of genes that protect against stress, to antioxidation and anti-inflammation.