Caloric Restriction Nutrition

Calorically restricted rats and mice are important tools for learning about basic biological processes that underlie aging. Indeed, the findings to date have focused research on the potential importance of oxidative stress in aging, and have also drawn attention to a possible role of blood glucose and insulin levels. Additionally, this research has provided further evidence of a relationship between resistance to stressors and retardation of aging.

Understanding the mechanisms underlying the antiaging action of caloric restriction could well yield insights on possible interventions for the retardation of human aging. The development of pharmacological agents with antiaging actions similar to those of caloric restriction is a particularly promising possibility. Even if long-term caloric restriction were conclusively demonstrated to extend life in humans, however, it is not likely many would undertake such a Spartan existence. Thus, there may be need for a more palatable regimen, such as a daily pill.

It is anticipated that research in the twenty-first century will focus on defining the mechanisms responsible for the antiaging action of caloric restriction. Genetically engineered mice are increasingly being used in this endeavor. In such mice, specific genes are either underexpressed or overexpressed. Although conceptually appealing, interpretations of such studies are problematic for at least two reasons. One, it will be a Herculean task for an investigator to establish that the mouse has been altered only in regard to the particular characteristic or characteristics being assessed. Moreover, the antiaging action of caloric restriction may be due to the action of more than one gene; if so, the manipulation of a single gene might provide little or no insight. The probability is infinitesimal that a mouse could be designed with the appropriate level of expression of several genes involved in the antiaging process.

Another new approach being increasingly used is gene expression profile methodology, in which a broad array of genes are assessed. In one such study, although only 5 to 10 percent of the genome was monitored, caloric restriction was found to affect the expression of more than one hundred genes. Thus assessment of the entire genome may find the expression of well over one thousand genes to be modified by caloric restriction. With so many genes influenced, it will be incredibly difficult to interpret the findings in regard to the mechanism(s) responsible for the antiaging action of caloric restriction.

For these reasons, it will be a formidable undertaking to determine the mechanisms of the antiaging action of caloric restriction, though the thoughtful use of currently available methodologies, as well the employment of new technologies, should eventually bring success.