. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature. 2002 Jul 18;418(6895):344-8. PubMed.

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  1. Eat Less, Live More —But Why? Comment by George Perry and Mark A. Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio USA

    A well lived life can only be seen in retrospect of a lifetime of living and, in the view of the ancient Greeks, by one of moderation. Scientific support for this view is found in the health benefits of a balanced diet rich in fruits and vegetables ( Lin et al., 2002; Luchsinger et al., 2002) with the greatest health benefit, and increase in longevity, coming from dietary restriction. In this regimen, organisms consuming around 30 percent of calories below ad libum have an approximately 30 to 50 percent increase in lifespan. Decreased free radicals, increased cellular stress, and altered hormonal balance are all thought to play a role but have not been confirmed by mechanistic studies. A link between Alzheimer disease (AD) and caloric intake has been made by case control studies showing that patients who go on to develop AD eat up to 500 more calories per day than controls in the decade prior to disease ( Smith et al., 1999.). Meta-analysis of world dietary habits shows that there is a strong correlation between the prevalence of AD and average caloric intake (( Grant et al., 1999.).

    The complexity of the relationship between diet, aging and AD has been made all the more apparent by recent studies. In evaluating the contribution of caloric and fat intake in AD, Mayeux and colleagues (Luchsinger et al., 2002) found high caloric intake was associated with an increased risk of AD. The risk was most significant for those people having at least one copy of the apolipoprotein E4 allele. In consideration that high caloric diets are usually rich in fats, these data are consistent with work by Petot and Friedland in which a link between fat intake and risk of AD was shown and, again, this was dependent on apolipoprotein -E genotype with E4 showing the most pronounced result (Friedland et al., 2002).

    Understanding the mechanism for increased risk from AD through high caloric intake may provide important insights into AD pathogenesis. The link between apolipoprotein-E genotype and fat intake suggests that lipid transport and metabolism may be critical to AD. Lessons might also be learned from studies of dietary restriction, which have been suggested to prolong lifespan through reduction of reactive oxygen formation, another mechanism involved in AD pathogenesis ( Perry et al., 1998). The recent finding of Lin and colleagues (2002), that the lifespan extending effect of dietary restriction relates to whether glycolysis or Krebs cycle metabolism dominates in yeast, is important because it suggests that it is not the total caloric intake but the outcome of dominance of one pathway or another that is critical to lifespan control. Therefore, caloric restriction may miss the point in that the consequences of differing metabolism strategies may have critical outcomes. Seen in light of the admonition for moderation by the ancient Greeks, it appears that the good life is not marked by extremes of diet but rather by a balance in metabolism.

    References
    Friedland RP, Petot GJ, Farrer LA (2002) Alzheimer’s disease and diet. Arab J Psychiatry, in press.

    Grant WB (2002) Dietary links to Alzheimer's disease. J Alzheimer’s Disease 1, 197-201.

    Lin S-J, Kaeberlein M, Andalis AA, Sturtz LA, Defossez P-A, Culotta VC, Fink GR, Guarente L (2002) Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418, 344-348. Abstract.

    Luchsinger JA, Tang M-X, Shea S, Mayeux R (2002) Caloric intake and the risk of Alzheimer disease. Arch Neurol 59, 1258-1263. Abstract.

    Perry G, Castellani RJ, Hirai K, Smith MA (1998) Reactive oxygen species mediate cellular damage in Alzheimer disease. J Alzheimer’s Disease 1, 45-55. Abstract.

    Smith MA, Petot GJ, Perry G (1999) Diet and oxidative stress: a novel synthesis of epidemiological data on Alzheimer’s disease. J Alzheimer’s Disease 1, 203-206. Abstract.

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  1. Caloric Restriction Increases Metabolic Rate