Models for Investigating How Dietary Restriction Retards Aging: The Adaptation Hypothesis

The studies reported by McCay et al. (1935) that dietary restriction (DR) initiated in early youth of rats extends both average and maximum life spans have been extended by numerous investigators (for comprehensive review see Weindruch and Walford 1988). Figure 22.1 schematizes the field of DR from both historical and conceptual standpoints. While there is a rough correlation between the time line and the “events” listed to the right of the time line in Fig. 22.1, I have made exceptions in order to improve the conceptual groupings [for example, Sacher (1977), Williams et al. (1987), and Hibbs and Walford (1989) all contributed to survival curve analysis, but at quite different periods]. From 1935 until the early 1970s essentially all studies of DR concerned its effect(s) on survival and/or diseases, especially tumors. From about 1972 on, and beginning with assessment of the effects of DR on the immune system (Walford et al. 1972, 1974), a major preoccupation of investigators has been with documenting the physiologic and “biomarker” effects of DR. Since the mid 1980s, the main emphasis has been the search for mechanisms. However, important studies are still ongoing in all these areas.