Dean Pomerleau Posted January 25, 2016 Report Share Posted January 25, 2016 Al Pater posted this older paper [1] 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 equivalencebetween DR in humans and DR in rodents. Instead, if our quantitative analysis is to betaken 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 longperiods 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 rodentsseems unappealing and ill-advised. Our conclusion is that it is reasonably prudentassuming that caloric restriction is unlikely to be a panacea for human aging. Boy they are Debbie Downers aren't they... --Dean ------------- [1] Ageing Res Rev. 2005 Aug;4(3):339-50. Why dietary restriction substantially increases longevity in animal models butwon't in humans. Phelan JP(1), Rose MR. Author information:(1)Life Sciences Core Curriculum Program, UCLA, Los Angeles, CA 90095-1606, USA.jay@ucla.edu 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 thelongevity-increasing effects of CR has prompted speculation that similar resultscould be obtained in humans. Longevity, however, is not a trait that exists in avacuum; it evolves as part of a life history and the physiological mechanismsthat determine longevity are undoubtedly complex. Longevity is intertwined withreproduction and there is a cost to reproduction. The impact of this cost onlongevity can be age-independent or age-dependent. Given the complexity of thephysiology underlying reproductive costs and other mechanisms affecting lifehistory, it is difficult to construct a simple model for the relationship betweenthe particulars of the physiology involved and patterns of mortality.Consequently, we develop a hypothesis-neutral model describing the relationshipbetween diet and longevity. Applying this general model to the special case ofhuman longevity and diet indicates that the benefits of caloric restriction inhumans would be quantitatively small. PMID: 16046282 Link to comment Share on other sites More sharing options...
Michael R Posted January 25, 2016 Report Share Posted January 25, 2016 You apparently don't remember, but I hacked this one to shit when it came out.Briefly, the main points are that:1. They take too seriously the notion, based on very indirect data, that the Okies were on severe, lifelong CR. As Willcox & co. were able to document,(1) however, they were actually only on about 10% CR, and their environmentally-imposed CR was alleviated by rising prosperity starting in the period between 1949 and 1961 if not before, when the famed centenarian cohorts were in their 50s-70s.2. They are also unaware of the influence of the Okinawans' mild malnutrition, also documented in (1), and ignore or were unaware of the poor medical care they received relative to the people to whom they are compared (the mainland Japanese (who have excellent health care), mainstream Americans, and sumo wrestlers (whose care is in most respects, I assume, even better than the Japanese population at large, since they're highly-paid elite athletes, as likely is their nutrition outside of energy intake). 3. They also take obesity/overfeeding as a straightforward extension of the energy continuum between severe CR, mild CR, and nonobese AL, which is problematic. Reference 1. Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, Suzuki M. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007 Oct;1114:434-55. PMID: 17986602 Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 25, 2016 Author Report Share Posted January 25, 2016 Thanks Michael, You apparently don't remember, but I hacked this one to shit when it came out. I figured you would have. As I said, I really wish the CR email list archives were available... [Edit by Brian: discussion of archives continued here.] I agree that there linear extrapolation of lifespan from both the high end (sumo wrestlers) and the low end (Okinawans) of the calorie intake continuum, without accounting for the very different life circumstances (e.g. healthcare and diet quality) of the different groups seems quite naive. --Dean Link to comment Share on other sites More sharing options...
Recommended Posts
Archived
This topic is now archived and is closed to further replies.