15 How Does Caloric Restriction Increase the Longevity of Mammals?

Abstract

The classic study by McCay et al. in 1935 showed that one could increase the life span of rats by reducing their food consumption. Since this initial observation, numerous laboratories have confirmed these results and have shown that reducing food consumption 30–50% (without malnutrition) consistently increases both the mean and maximum life spans of laboratory rodents (Weindruch and Walford 1988; Masoro 2005). Caloric restriction is also able to oppose the development of diverse age-associated diseases arising in laboratory rodents, including many types of cancer, diabetes, and renal disease (Weindruch and Walford 1988). This paradigm has been termed caloric restriction, dietary restriction, or food restriction. In this chapter, we use the term caloric restriction (CR) because the decreased intake of total calories appears to be responsible for the increased life span of rodents (Masoro 2005), rather than the reduction in a specific nutrient, such as dietary protein or fat (Iwasaki et al. 1988; Masoro et al. 1989). It is important to note that the effect of CR on longevity is not limited to rodents, as it increases the life span of a variety of invertebrates, e.g., yeast, Caenorhabditis elegans, and Drosophila (Min and Tatar 2006), as well as of dogs (Kealy et al. 2002). In this review chapter, we focus on what currently is known of the biological mechanism responsible for the life-extending action of CR in mammals, specifically laboratory rodents and nonhuman primates.

LABORATORY RODENTS
Since the seminal observation by McCay et al. in 1935, CR has been shown...