History of caloric restriction, aging and longevity

Abstract

In 1935 Clive McCay and his colleagues published a seminal paper, which showed that slowing the post-weaning growth of rats by markedly restricting their food intake significantly increased their longevity. Since then global food restriction has been found to increase the length of life of a spectrum of rat and mouse strains and of several non-mammalian species. McCay and colleagues proposed that the basis of this life extension was the slowing of growth. This hypothesis went unchallenged until 1960 when Berg and Simms proposed that the life extension was due to the reduction in body fat content. Starting in the 1970s a series of different hypotheses have been proposed to be the mechanism underlying the life extension. However, to date there is not a general agreement regarding the biological basis. In the years following the seminal 1935 paper, it was shown that the nutritional factor underlying the life extension is the reduction in energy intake; thus the term caloric restriction (CR) has been widely used when referring to this phenomenon. Over the years, CR has been reported to retard a spectrum of age-associated diseases and the aging of many physiological processes. Also, hypotheses on the evolution of the life extending action have been proposed. Prior to the 1990s, morphological pathology and physiology were the primary tools used to explore CR. However, during the past two decades, molecular biology has been increasingly put to use in the effort to understand the basis of the CR's actions.