The Retardation of Aging in Mice by Dietary Restriction: Longevity, Cancer, Immunity and Lifetime Energy Intake

Abstract

We sought to clarify the impact of dietary restriction (undernutrition without malnutrition) on aging. Female mice from a long-lived strain were fed after weaning in one of six ways: group 1) a nonpurified diet ad libitum; 2) 85 kcal/wk of a purified diet (approximately 25% restriction); 3) 50 kcal/wk of a restricted purified diet enriched in protein, vitamin and mineral content to provide nearly equal intakes of these essentials as in group 2 (approximately 55% restriction); 4) as per group 3, but also restricted before weaning; 5) 50 kcal/wk of a vitamin- and mineral-enriched diet but with protein intake gradually reduced over the life span; 6) 40 kcal/wk of the diet fed to groups 3 and 4 (approximately 65% restriction). Mice from groups 3-6 exhibited mean and maximal life spans 35-65% greater than for group 1 and 20-40% greater than for group 2. Mice from group 6 lived longest of all. The longest lived 10% of mice from group 6 averaged 53.0 mo which, to our knowledge, exceeds reported values for any mice of any strain. Beneficial influences on tumor patterns and on declines with age in T-lymphocyte proliferation were most striking in group 6. Significant positive correlations between adult body weight and longevity occurred in groups 3-5 suggesting that increased metabolic efficiency may be related to longevity in restricted mice. Mice from groups 3-6 ate approximately 30% more calories per gram of mouse over the life span than did mice from group 2. These findings show the profound anti-aging effects of dietary restriction and provide new information for optimizing restriction regimes.

Explaining longevity of different animals: is membrane fatty acid composition the missing link?

“…A recent study in mice has shown that changes in membrane composition are both proportional to the degree of CR and manifest within 1 month of onset of CR (Faulks et al 2006). Figure 4b illustrates the changes in PI of liver mitochondrial membranes of these mice relative to the changes in maximum longevity previously reported by others in a different mice strain but using the same CR regime (Weindruch et al 1986). …”

“…This treatment is the most common manipulation in the study of aging and was first described for rats in 1935 (McCay et al 1935). The degree of life span extension is linearly related to the amount of CR in both rats (Merry 2002) and mice (Weindruch et al 1986), but the precise mechanism by which CR extends longevity is not known (Masoro 2002). A common finding is that lipid peroxidation is reduced during CR (Habib et al 1990;Matsuo et al 1993).…”

“…In a, the new fatty acid data points in this figure are for the mouse strains (filled circles) and are taken from Hulbert et al 2006a while the life span data are from Miller et al 2002. In b the new fatty acid data points for CR mice (filled circles) and are from Faulks et al 2006 while the life span data are from Weindruch et al (1986) Fig. 5 Comparison of the PI of phospholipids from pollen and different life stages of the honey bee (Apis mellifera).…”

Mitochondrial DNA repair in aging and disease

“…Calorie restricted rodents have a longer lifespan than their ad libitum fed counterparts (85). A recent human trial showed that caloric restriction resulted in the expected reduction in body weight and blood insulin (86).…”

Dietary restriction modulates synaptic structural dynamics in the aging hippocampus

“…Despite many hypotheses, so far all have failed to explain the mechanism of action of different food restriction schedules, it remains well proven that the function organ systems are better and longer preserved in dietary restricted animals. Namely, the immunological response is markedly improved (4), renal and myocardial diseases (5) as well as the incidence of tumor mediated by free radicals (6,7) are reduced in food restricted animals.…”