From: ((Steven B. Harris)) Subject: Re: Sci.life-extension Calorie Restriction FAQ Date: 07 Jun 1995 In <3r328q$ct@soenews.ucsd.edu> barry@starfire.ucsd.edu (Barry Merriman) writes: >I'm curious as to exactly how lifespan varies with >caloric intac in CR experiments. Its not clear exactly what >the caloric variable should be, but either calories consumed >per unit of time (e.g. calories per day) or total calories >consumed during the lifetime would be reasonable choices. Does >one obtain some characteristic graph of lifespan vs. either of >these variables? In particular, do you die after eating a certain >number of calories? Answer: Well, mice on CR get far more calories/gram of mouse/lifetime than do fully fed ones. They do get about the same number of calories per mouse per lifetime, due to being smaller. I suspect that CR initiated at weaning is a different kind of thing than CR initiated in young adulthood, and probably has additional mechanistic effects (perhaps developmental clock effects as well as energy/ metabolic effects). Weening-CR results in mice which are structurally different, with most organs (though not, significantly, the brain) smaller in weening CR mice. Life extention here is radically longer. By contrast adult restriction results in much less life extension (even calculated on the basis of lifetime calories), and body composition changes showing radical fat loss (and I suspect probably slower specific metabolic rate), but not greatly decreased size of vital organs. Steve Harris, M.D. >-- >Barry Merriman >UCSD Fusion Energy Research Center >UCLA Dept. of Math >bmerriman@fusion.ucsd.edu (Internet; NeXTMail is welcome) From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: Calorie Restriction and Exercise (was The Exercise Paradox) Date: 3 Nov 1998 09:54:01 GMT In <363E977D.96960BA8@notarealaddr.ess> Brian Manning Delaney <bmdelaney@notarealaddr.ess> writes: >Holloszy's most recently published study provides the extra >Calories to CR'd exercisers. In the previously (repeatedly) >established relationship among the three variables, exercise, >degree of restriction, and longevity, C and D, below, differ >appreciably. In Holloszy's lastest study (and in the other one I >cited) they look quite similar, but extra Calories to group C >were provided (or fewer to D, depending on how you look at it): > >A. Non-CR'd, sedentary rodents. (Shortest-lived.) >B. Non-CR'd, exercised. (Between) >C. CR'd and exercised. (Longest-lived.) >D. CR'd and sedentary. (Longest-lived.) > >Holloszy's most recent study (not the one I referred to in the >previous post) fed group D to be WEIGHT-matched with group C. >They ate a lot less food. Group C was restricted by 30%. Group D >ended up being restricted by about 50%. Yet the difference in >mortality was not significant (the most long-lived of D lasted a >tiny bit longer than the most long-lived of C). > >Holloszy speculates, however, that with a different strain the >same results might not apply. The reason he gives is that in the >strain used here, the Long Evans rat, CR beyond 30% doesn't >produce additional significant life span gains -- at least his is >what he found in his previous study [2]. > >Either way, if this finding proves repeatable, it weakens the >idea that exercise is not good for people on severe CR. > >Best wishes, >Brian. Very interesting. It also strengthens what some of us have long thought, which is that CR is not just a matter of "decrease in calorie generated free radicals". Rather, the driving factor is some metabolic consquence (hormones, temperature, glucose, etc) of the body weighing less than it wants to, so that it thinks it is starving. Body composition (the ob/ob mouse data) and exercise, and indeed, even total caloric intake, are almost irrelevent. If you can run more calories through without changing the body's relationship to its own striven-for "set point", you'll get the same life span extending effect. Yes, the experiment needs to be repeated to see if the relationship is between calories taken in and calories the body WANTS to take in (so that the excercised group has the chance to show even more effect). But I doubt it will happen. I don't think the body really has any way to know how many calories have been eaten. It only knows how much storage energy is available at any given time, and (of course) also how well the homeostatic mechanisms are keeping up with the necessity to maintain body temperature. SBH ------------------------------------------------------------------- "I know of no better life's work than to run the insignificant and easily destroyed newgroup opinion to ground." -- Usenet Addicts Anonymous. Credo #1 -------------------------------------------------------------------- From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: EU vitamin ban -can cutting vitamin intake be dangerous? Date: Mon, 25 Mar 2002 10:47:01 -0800 Message-ID: <a7nr90$3pe$1@slb3.atl.mindspring.net> michaelprice wrote in message <4ABn8.18030$Dr3.2460445@news6-win.server.ntlworld.com>... >Steve's "controls" - for which criticism (a) applies!! - were on 10% >restriction. Tragic since CR improves glucose tolerance. Actually, it doesn't (at least in mice): you should see the glucose tolerance curves in my 40% CR animals-- horrible (abstract is below, but it really takes looking at the graphs to get the full impact). Being on severe CR doesn't give you a pancreas with a lot of reserve (not surprisingly). It's the average and fasting glucoses that are low in CR. 10% gives intermediate fasting glucoses, and the best glucose tolerance to acute challenge. Ad lib animals are pre-diabetic. Incidentally I did run some of these on Cr picolinate for a while and got no glucose effect. I couldn't get ANY effect of this stuff in my model on ANY parameter. Thanks to Michael for answering the other parts of your question and doing a lot of work for me. I will add only that the literature of gerontology is litered with claims for life span improving properties of all kinds of things: Vitamins C and E, DMAE, cysteine, cysteamine, BHT, ethoxyquin, deprenyl, CoQ10, lots of other stuff. It proved to be unrepeatable, by and large. I don't even completely believe my own results until they've been confirmed; it's too easy to fool yourself in science. There are also old reports from the 40's, 50's and 60's like the ones you cite: never confirmed and there they sit. My guess is that if they were repeatable they also would have been confirmed. Since they haven't, we can ignore them. If you want to try repeating them yourself and maybe be famous, be my guest. Mech Ageing Dev 1994 Mar;73(3):209-21 Related Articles, Books, LinkOut Serum glucose, glucose tolerance, corticosterone and free fatty acids during aging in energy restricted mice. Harris SB, Gunion MW, Rosenthal MJ, Walford RL. Department of Pathology, University of California at Los Angeles 90024. Energy restriction, the only method known to increase maximum life span in laboratory animals, was used as a tool to test hypotheses regarding possible mechanisms of aging. Serum glucose and corticosterone (CS) concentrations in mice of a long-lived hybrid mouse strain, aged 7, 17, and 29 months, and on 50%, 80%, and 100% of ad libitum intake, were measured. Serum glucose and CS concentrations were also measured in response to intraperitoneal (i.p.) glucose challenge in mice at ages 7 and 29 months. Serum glucose and CS concentrations were also measured at several time points over 36 h, to assess their diurnal variation. There were no differences in single fasting glucose concentrations in 7- and 29-month-old mice at the same degree of energy restriction, but energy restriction decreased glucose concentrations. Serum CS concentrations were generally increased restricted animals with respect to fully fed ones. Average serum glucose concentrations were found to be significantly decreased by dietary restriction. Glucose tolerance curves were unchanged by age in ad libitum fed or 50% restricted animals, but in 80% ad libitum groups, older animals showed evidence of decreased glucose tolerance with respect to young animals. For each age, peak serum glucose concentrations after i.p. glucose loading varied with degree of energy restriction, with more severely restricted animals showing less glucose tolerance. Average serum CS concentrations were elevated at 7 months by restriction, especially at night and long after feeding, but we found no differences with age or diet in average CS concentrations. Our serum glucose results support the hypothesis that nonenzymatic glycation is mechanistically involved in normal aging. Our serum CS results do not support the hypothesis that CS contributes significantly to the pathophysiology of normal aging in mice. PMID: 8057691 [PubMed - indexed for MEDLINE] -- I welcome email from any being clever enough to fix my address. It's open book. A prize to the first spambot that passes my Turing test. From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: EU vitamin ban -can cutting vitamin intake be dangerous? Date: Mon, 25 Mar 2002 15:21:47 -0800 Message-ID: <a7obc7$rt4$1@slb6.atl.mindspring.net> michaelprice wrote in message ... >> Actually, it doesn't (at least in mice): you should see the glucose >> tolerance curves in my 40% CR animals-- horrible (abstract is below, >> but it really takes looking at the graphs to get the full impact). Being >> on severe CR doesn't give you a pancreas with a lot of reserve >> (not surprisingly). >> It's the average and fasting glucoses that are low in CR. 10% gives >> intermediate fasting glucoses, and the best glucose tolerance to acute >> challenge. Ad lib animals are pre-diabetic. Incidentally I did run >> some of these on Cr picolinate for a while and got no glucose effect. > >Old, young or both? Both as I recall. >> I couldn't get ANY effect of this stuff in my model on ANY parameter. > >Including insulin levels? I didn't look at that. My assay for insulin was not the most sensitive, and I really couldn't reliably "see" any fasting insulin level differences even among various fasting restriction groups. I saw a clear insulin signal only with glucose challenge, and didn't look at glucose tolerance with chromium. >You really should publish since it is impossible to critique unpublished >word-of-mouth stuff. Yep. -- I welcome email from any being clever enough to fix my address. It's open book. A prize to the first spambot that passes my Turing test. From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: EU vitamin ban -can cutting vitamin intake be dangerous? Date: Sun, 31 Mar 2002 20:04:11 -0700 Message-ID: <a88je0$5i7$1@slb4.atl.mindspring.net> "michaelprice" <michaelprice@ntlworld.com> wrote in message news:2uMp8.31201$gj7.4928174@news2-win.server.ntlworld.com... > Second, the lower fasting glucose levels of Steve's CR "controls" is also > an effect produced by chromium picolinate, so they are not good controls. How do you you figure? The CR animals got the same amount of brewer's yeast per animal per day as the others. Believe me, little bits of brewers yeast give or take make no difference in this system. We tried giving non restricted and slightly restricted mice a lot more of brewer's yeast; and we tried giving them a hellava lot of straight red Cr-picolinate powder ("Chromax II"), as the pure chemical provided from the nice people at Nutrition 21 in La Jolla, CA, 12.5% chromium by weight (I'm sitting here, looking at the bottle as I type). And we did both. There was no effect on glucose whatsoever. The restriction effect on glucose is NOT a chromium effect. If it were, we've have swamped it 3 ways from Sunday. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: EU vitamin ban -can cutting vitamin intake be dangerous? Date: Mon, 1 Apr 2002 10:23:24 -0700 Message-ID: <a8a5g8$gp2$1@slb1.atl.mindspring.net> "michaelprice" <michaelprice@ntlworld.com> wrote in message news:TeTp8.34766$gj7.5248199@news2-win.server.ntlworld.com... > "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> wrote in message > news:a88je0$5i7$1@slb4.atl.mindspring.net... > > "michaelprice" <michaelprice@ntlworld.com> wrote in message > > news:2uMp8.31201$gj7.4928174@news2-win.server.ntlworld.com... > > > >> Second, the lower fasting glucose levels of Steve's CR "controls" > >> is also an effect produced by chromium picolinate, so they are > >> not good controls. > > > > How do you you figure? The CR animals got the same amount > > of brewer's yeast per animal per day as the others. > > Sorry, you'll have to clue me in here. Brewer's yeast was used as > a source of B-vitamins or chromium GTF? Of GTF only. We had suspicions about the CrCl3 (as I remember) being used in the AIN-76 mineral mix of the time. Or perhaps there was no Cr at all in that mix-- I no longer remember. Anyhow restricted animals got about 60% of the food of ad lib animals, so they were given a diet which was more dense in vitamins, minerals and yeast by a factor of 1/0.6 = 5/3. > Another thought, is the > strain you used susceptable to diabetes, like humans? Not really. The ad libs ran glucoses around 120 mg/dL, which wouldn't formally give them the diagnosis, even in todays' more conservative atmosphere (where you need to be above 129). Perhaps a few were above 129, but we'd have ignored them since the criteria then was 139. As a group, old ad-lib fed C57Bl10/C3H hybrids are near diabetics, at best. For a real diabetic, this control would be excellent with A1c's in the 6's. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,misc.health.alternative,alt.health Subject: Re: CR Research Update Date: Mon, 8 Apr 2002 15:56:11 -0600 Message-ID: <a8t3lr$rus$1@slb6.atl.mindspring.net> "Ian Goddard" <igoddard@erols.mom> wrote in message news:3cadb458.31640034@news.erols.com... > IAN: McCay's findings were not seen as discovering a method > of anti-aging. It was assumed that what was happening with > life-long CR was that by delaying the onset of puberty, all > the subsequent phases of life were delayed, including death. Not everybody assumed that. Even McCay, if I am to credit hearsay. I once, 10 years ago at UCLA, heard a lecture by gerontologist James E. Birrin, in which he mentioned that he's served in WWII aboard a destroyer with the very same Clive McCay, and McCay spent a lot of time telling people they would do better to eat less if they wanted to live longer! That's a hell of a good story, if true. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,alt.health,misc.health.alternative,sci.med Subject: Re: CR & Fasting Date: Sun, 16 Jun 2002 22:13:40 -0600 Message-ID: <aejo1p$djq$1@slb6.atl.mindspring.net> "Ian Goddard" <igoddard@erols.mom> wrote in message news:3d0ce20c.42516749@news.erols.com... > On Sun, 16 Jun 2002, Tom Matthews <tom@morelife.org> wrote: > > >Ian Goddard wrote: > > > >> This soon-to-be published study just posted to the crsociety list > >> presents strong evidence contrary to the case I made aginst fasting: > >> > >> http://www.americanaging.org/abs/Anson2.htm > >> > >> The study suggests that every-other-day fasting yields life-extension > >> effects comparable to daily-feeding CR but with only a 9% reduction > >> in total caloric intake. COMMENT No, as this study did not look at life span directly, but only very dubious markers. Do not take wooden nickels in this game-- the *only* gold standard in calorie restriction studies is life span. Yes, this study CLAIMS that you can get the same life span by every other day (EOD) ad lib feeding as by (some other level) of caloric restriction. I know of no evidence that every other day feeding gives you any life span advantage at all over any other kind of feeding which results in the same calorie intake (which is a bit less than total ad lib, as noted, but not that much less). EOD ad lib feeding is a very mild sort of CR, but it only produces mild CR effects also, if you do it ad lib. Nobody has yet been able to reproduce the tremendous effects of the 82 Goodrick paper. At Walford's lab the restricted animals got fed 3x per week, to be sure, but that was only a matter of convenience-- their portions on the days they were fed were restricted. Even the "ad lib" animals only got fed 5x a week, with a double portion before the weekend (which they ate in 12 hours) after which they went 2 days without anything. They were big fat animals and didn't get any life span extension by comparison with known curves for that breed. >>This of course immediately suggests that > >> the effects of CR may come from periods of food depravation per se > >> rather than from (or only from) an overall reduction of calories. COMMENT: Not until we see a LOT more data, it doesn't! Remember, we haven't all been running out to do feeding frequency studies in DR, because enough of them have already been done to suggest that time-between-meals is not a big part of the answer. In the 90's we were all aware of the Nelson and Halberg study quoted below. I wrote a bunch of grants in the early 90's to do much the same work you see that Masoro finally did in 1995 below (mine got turned down, his obviously didn't). More or less, Masoro failed to find any effect either between once a day and twice a day restriction. Nelson, as a bit of trivia, had to build a cute little machine which was basically a gear and clock driven Archimedes screw which delivered tiny powder meals 6x a day, but totaling out to an energy restricted diet. He got the full CR effect anyway. IAN: > The following is from a reply I made on the crsociety list... > > > IAN: Yeah, I wasn't able to find any research testing EOD vs > daily-feeding CR. While the study at the AAA site is not yet > published, the NIA researchers are a reliable group, I would > take their findings at face value. Yep. IAN: >The fact that we cannot > find any head-to-head tests also means we have nothing that > suggests their findings are questionable. Harris: Burden of proof is on them. They are not doing what anybody these days would call "CR," so it remains up to them to show it is a significantly life span prolonging therapy. They can't just cite one paper from 1982. IAN > I was not able to find any studies showing that EOD extended > Maximum LS, but I would be surprised if there was a difference > in this respect between EOD and LDF mice that went unmentioned > in the abstract. These researchers know CR and would most surely > observe mean vs max LS and note any differences. I found these: > > 6641783: "...EOD-fed rats had a mean lifespan of > 124 weeks compared to 103 weeks for AL-fed rats." But would be expected to have a slightly smaller food intake. > 7117847: "The mean life span of the EOD group > represented an 83% increase over that of the AL group." COMMENT: This is the Goodrick et al paper of 1982, and it probably represents the best findings for EOD ad lib in the literature. Even here, though, the EOD animals weight less, so were somewhat restricted. ================== J Nutr 1986 Nov;116(11):2244-53 Meal-timing, circadian rhythms and life span of mice. Nelson W, Halberg F. The possibility that circadian rhythm alteration may contribute to the life-prolonging effect of food restriction was investigated in female CD2F1 mice housed in a room with a 12-h span of fluorescent lighting daily. A control group was allowed to feed ad libitum throughout life while three other groups began lifelong restriction to about 75% of ad libitum intake when 6 wk old. The daily schedule of food accessibility differed among these three groups: a single meal during early darkness; a single meal during early light; six smaller meals at about 2-h intervals during darkness. Food restriction as such clearly prolonged life, but there were no statistically significant differences in overall mean life span or in 10th-decile life span among the three restricted groups. Telemetered body temperature data confirmed marked differences in the effects of these different restricted feeding schedules on circadian rhythms. The effect of food restriction on survival is probably not due to altered relations among circadian rhythmic variables. Possible contributing factors suggested by the results are a lower body temperature, a reduced overall metabolic rate and an increased circadian amplitude. PMID: 3794831 [PubMed - indexed for MEDLINE] =================================== J Gerontol A Biol Sci Med Sci 1995 Jan;50A(1):B48-53 Temporal pattern of food intake not a factor in the retardation of aging processes by dietary restriction. Masoro EJ, Shimokawa I, Higami Y, McMahan CA, Yu BP. Department of Physiology, University of Texas Health Science Center at San Antonio. Long-term dietary restriction programs which retard aging processes in rodents usually involve meal eating rather than the nibbling pattern of food intake of ad libitum fed rodents. Thus, the possibility arises that the antiaging action may at least in part result from an altered temporal pattern of food intake. This possibility was investigated using male F344 rats maintained on the following dietary regimens: Group A rats fed ad libitum; Group B rats fed 60% the ad libitum intake in a single meal at 1500 h; Group B-2 rats fed 60% of the ad libitum intake in two meals (0700 h and 1500 h). The diurnal pattern of plasma corticosterone concentration differed among the groups as did that of the plasma glucose concentration. The median length of life and age of tenth percentile survivors were similar for Group B and B-2 rats and much greater than those for Group A rats. Both modes of dietary restriction influenced age-associated disease processes in a similar fashion. Thus, although the temporal pattern of food intake influenced circadian rhythms of food-restricted rats, it did not significantly affect the antiaging action. PMID: 7814779 [PubMed - indexed for MEDLINE] SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: soc.support.fat-acceptance,alt.support.big-folks,soc.singles, alt.support.diet,sci.med Subject: Re: Massive study links excess weight, cancer risk Date: Thu, 24 Apr 2003 14:24:59 -0700 Message-ID: <b89kn9$c7j$1@slb6.atl.mindspring.net> "Crazy Mullet" <jadey@my-deja.com> wrote in message news:VMWpa.114801$MB4.39768002@news4.srv.hcvlny.cv.net... > "The morbidly obese are harder to operate on, harder to plan radiation > therapy for -- often, they don't even fit into a radiation therapy > machine," Mayer said. He said it also is hard to decide the right > chemotherapy dose for the obese, because fat tissue sometimes absorbs > the chemicals." > > I don't see this as being a hunch. > > Jade Calorie restriction as long been known as an anti-aging treatment in lab animals (rodents, and now also primates). It is known that much if its life-prolonging effects are due to its cancer preventative properties for many kinds of tumors. As Ben Franklin said: "To lengthen thy life, lesten they meals." SBH |
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