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Dean Pomerleau posted a topic in CR Science & TheoryAl Pater posted this older paper  that I don't believe has been discussed here before - perhaps on the email list, but unfortunately those archives aren't available... It has the pessimistic title: "Why dietary restriction substantially increases longevity in animal models but won't in humans". In it, the authors develop a simple (simplistic?) linear model of the impact of calorie restriction on rodent longevity - as long as calories remain above a certain minimum needed for survival, their model say a given percentage decrease in calories will result in the same percentage increase in lifespan. They use rodent CR data from a range of experiments to create this model, and claim their model fits the data pretty well - which isn't too surprising. Although recent data and analysis discussed here, suggests that in rodents (and primates) that a disproportionate fraction of CR longevity benefits may be achieved via modest (e.g. 10%) restriction, suggesting such a linear model of benefits may not be appropriate. Then they try to apply the same model to humans, by fitting a linear model to three different populations of Japanese people whose calorie intake and lifespan information we know - long-lived male Okinawans who eat ~1900kcal/day, medium-lived average Japanese men who eat 2300kcal/day, and short-lived Sumo wrestlers who eat 5500kcal/day. By their best estimate, fitting a line between the Sumo wrestlers and the normal japanese men, they come up with a very modest, 7% (or 5 year) lifespan extension for lifelong, maximal CR (which they estimated to be 1500kcal/day) relative to lifespan eating a normal diet of 2300 kcal/day. They argue that the reason rodents see such a large benefit (up to 64% life extension) from CR while humans will likely enjoy such a small benefit is because of the different fractions of energy the two species devote to reproduction. In short, relative to "normal" fecund & well-fed rodents, CRed rodents can tolerate a crushing 66% CR (yes - only 33% of "normal" calorie intake), because of all the energy they can save by not 'wasting' energy on reproductive functions. In contrast, humans devote a much smaller fraction of our energy budget to reproduction, and so can tolerate a much smaller degree of CR than rodents. Not to mention we have free access to food and the rodents can only eat what the cruel researchers put in their cages - one rodent per cage to avoid cannibalism... They go on to editorialize about the relatively futility of human CR, saying: Caloric restriction is likely to be almost universal in its beneficial effects on longevity. This does not, however, warrant an expectation that there will be a quantitative equivalence between DR in humans and DR in rodents. Instead, if our quantitative analysis is to be taken at face value, the quantitative benefit to humans from caloric restriction is going to be small, even if human subjects restrict their caloric intake substantially and over long periods of time... To undergo decades of CR, suffering chronically reduced fertility and increased hunger, for the sake of a much smaller proportionate increase in longevity than is seen in rodents seems unappealing and ill-advised. Our conclusion is that it is reasonably prudent assuming that caloric restriction is unlikely to be a panacea for human aging. Boy they are Debbie Downers aren't they... --Dean -------------  Ageing Res Rev. 2005 Aug;4(3):339-50. Why dietary restriction substantially increases longevity in animal models but won't in humans. Phelan JP(1), Rose MR. Author information: (1)Life Sciences Core Curriculum Program, UCLA, Los Angeles, CA 90095-1606, USA. email@example.com Full text: http://roselab.bio.uci.edu/Publications/75%20Phelan%20Rose%202005.pdf Caloric restriction (CR) extends maximum longevity and slows aging in mice, rats, and numerous non-mammalian taxa. The apparent generality of the longevity-increasing effects of CR has prompted speculation that similar results could be obtained in humans. Longevity, however, is not a trait that exists in a vacuum; it evolves as part of a life history and the physiological mechanisms that determine longevity are undoubtedly complex. Longevity is intertwined with reproduction and there is a cost to reproduction. The impact of this cost on longevity can be age-independent or age-dependent. Given the complexity of the physiology underlying reproductive costs and other mechanisms affecting life history, it is difficult to construct a simple model for the relationship between the particulars of the physiology involved and patterns of mortality. Consequently, we develop a hypothesis-neutral model describing the relationship between diet and longevity. Applying this general model to the special case of human longevity and diet indicates that the benefits of caloric restriction in humans would be quantitatively small. PMID: 16046282