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Anti-aging by caloric restriction

Discussion in 'Topics in Healthcare' started by USCguy, Feb 15, 2006.

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  1. USCguy

    USCguy Earnest Internist 10+ Year Member

    Nov 3, 2005
    Has anyone read any of the studies in animals using caloric restriction (but with proper nutrition) to study longevity?
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  3. FutureDocDO

    FutureDocDO 1K Member 10+ Year Member

    Apr 20, 2004
    Yes. It slows down the rate of cell division and as such it takes longer for telomeres to shorten to the critical point. Studies have shown that you can increase your life expectancy by reducing your caloric intake but the downside is you will not have much energy to do anything. Live longer but less of a life.
  4. Shredder

    Shredder User 5+ Year Member

    Dec 14, 2004
    yeah its pretty well documented i think. for humans i believe the caloric intake has to be between 1000-1500 for life to see marked extension. definitely a sacrifice of quality for quantity. but im with you if you want to explore more luxurious methods of life extension. theyve studied it in rats or mice a lot--partial starvation i mean. me and a friend of mine are all about the idea of telomerase bars and cereal
  5. Moxxie

    Moxxie Rained out 7+ Year Member

    Oct 20, 2005
    Temperate Rainforest
    Hey there -

    I work in one of the primary research labs that studies caloric restriction in transgenic and knockout mice (I actually manage the mouse colonies). Studies so far have shown that CR is the number one way to extend lifespan in rodents. I emphasize this because effective studies on humans/other primates have not been completed. The amount of restriction required to extend lifespan, however, is not trivial - usually 60% or more (as in, the animals consume only 60% of their normal calories). We're not sure yet WHY exactly CR extends lifespan - telomere length was mentioned by a previous poster, but I honestly think that telomeres have been overplayed in the media. Not that they aren't important, but oxidative stress is a MUCH bigger player in aging.

    If you're interested in this, use pubmed to look up research done by Arlan Richardson and other labs at the University of Texas HSC in San Antonio. Specifically, researchers associated with the Barshop Institute for Longevity and Aging Studies. USC has a bunch of researchers that study aging/caloric restriction as well.
  6. medworm

    medworm Senior Member 5+ Year Member

    May 17, 2004
    There's also Dr. Roy Walford at UCLA, who practiced and researched CR for years.
  7. jonathon

    jonathon Banned Banned

    Dec 28, 2005

    There is evidence that ROS can damage the telomerase. This may be the reason why the cells on people who run multiple miles everyday have wrinkled skin and age faster in their skin appearance.

    The person who posted that you will have a depleted energy state with a CR diet is wrong. You have to eat the correct organic food sources to get the energy sources that can equate to a person on a 2,000 calorie diet. It can be done. It just takes focus.
  8. USCguy

    USCguy Earnest Internist 10+ Year Member

    Nov 3, 2005
    When you say "ROS" are you talking about oxidative damage to the cells of the people running everyday. If so, I guess the first foundation of this would have to be loading up on all the vitamins/anti-oxidants out there...maybe eating a predominantly vegetarian diet would do the trick...plenty of cruciferous veggies and sweet potatoes. I guess this would some what fall in line with the present food guide pyramid recommendations.
  9. jonathon

    jonathon Banned Banned

    Dec 28, 2005
    ROS has a known mechanism of being a second messenger (H202) in various signal transduction responses ranging from proliferation to growth or differentiation arrest to senescence and cell death by activating signaling pathways that include phosphoinositide 3-kinase, NF-B, phospholipase C-1, p53, CREB, HSF, and mitogen-activated protein kinases.

    Sources of ROS: mitochondrial respiratory chain, activated leukocytes, cigarette smoke, radon, ozone, and UV rays.

    Oxidative Damage to: DNA, lipids, proteins

    Contribution to: aging, heart disease, cancer, Alzheimer's disease, inflammatory/autoimmune diseases (diabetes), AIDS, and adult respiratory distress syndrome.

    You are correct about the antioxidants. However, it also depends on the type of antioxidant molecule that is being consumed. Not all antioxidants interact the same with ROS.
  10. QuikClot

    QuikClot Senior Member 5+ Year Member

    Nov 20, 2005
    This was an early theory for why calorie restriction works; it's no longer in vouge. From Scientific American:

    If true, this is the best news possible; it means that CR is not the cause of extended lifespan, but rather it is a hostile enviroment that the body recognises as such and extends the lifespan of the organism.

    This means we ought to be able to activate the genes and extend our lives without starving ourselves.

    It is also very promising that the trade-off appears to be decreased fertility. Obviously, there must be some evolutionary reason that these genes aren't on all the time. And we all know how evolution feels about decreased fertility. From the human point of view, however, it is a very managable side effect (we could do with a few fewer people on the globe, for that matter!)

    After reading this article, I really think they can do it; extend not just our lives but our prime of life (what the eggheads call anti-senescence) with a simple pill regime (they even have a canadidate! It's called resveratrol. (In addition to the article, see

    Not intrigued? Did I mention it's implicated in fat storage . . . so it makes you lean and muscular as well as long-lived?

    Of course this could all go the way of the flying car. Personally, after seeing this article, I'm re-deadicating myself to a healthy lifestyle; I want to live long enough to live even longer.
  11. jonathon

    jonathon Banned Banned

    Dec 28, 2005
    Hi quickclot,

    You did a good job! You are correct in all phases of your analysis. However, try to let the evidence speak for itself. There are drawbacks, though, with the thought of just being able to activate high expression levels of certain genes. Gene expression is highly regulated. So a lot of research is needed to be done to see the results of tweaking the gene expression levels. There is also lack of evidence to date that shows that this method will work in all population groups. Slowing down the metabolic reactions in an organism is not known if it is beneficial in the long run.

  12. QuikClot

    QuikClot Senior Member 5+ Year Member

    Nov 20, 2005
    A few things:

    * The tone of your reply is rather patronizing. If I wake up some morning and I feel the need for your validation, I'll let you know.

    * Of course more research is needed. And it is ongoing. We are at the stage of musing, speculating, hoping and scheming; all of which are healthy spurs to the process of innovation and discovery.

    * "Letting the evidence speak for itself" is a non sequitur. Evidence doesn't speak. People do. Scientists are storytellers who try and tell stories that fit the facts.

    * These genes do not, as far as is known, slow down the metabolism. CR, as far as we know, does not, and the mooted protective mechanisms do not imply that.

    * It is not necessary to say "we don't know if it will work for all groups" when my own sources say that prominiantly. I have read my own sources. We don't know if these genes exist in humans, but since they exist in flies, flatworms, and fish, my money says that we will find them throughout the animals.
  13. jonathon

    jonathon Banned Banned

    Dec 28, 2005
    FYI: I study Human genetics.

    Obviously you don’t know what is meant by let the evidence speak for itself.

    Genes do have roles in metabolism. The molecular clock genes influence metabolism of sugar and dietary fats. The genes yiaP and yiaR of the yiaKLMNOPQRS have a role in the metabolism of the endogenously formed L-xylulose. The CYP50 genes have a role in metabolism in the liver that function as “oxidative metabolism.” There are a lot of other examples that I can share but I will just leave it as this.

    You should read up on metabolic disorders.

    You are better of reading primary journals and not second hand information from a lay magazine.

    Population studies are important on this subject. I won't get into it though since I need to get to the lab. <>

  14. jonathon

    jonathon Banned Banned

    Dec 28, 2005
    Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila
    William Mair1, Matthew D. W. Piper1, Linda Partridge1*

    1 Centre for Research on Ageing, University College London, Department of Biology, London, United Kingdom

    Dietary restriction (DR) extends life span in diverse organisms, including mammals, and common mechanisms may be at work. DR is often known as calorie restriction, because it has been suggested that reduction of calories, rather than of particular nutrients in the diet, mediates extension of life span in rodents. We here demonstrate that extension of life span by DR in Drosophila is not attributable to the reduction in calorie intake. Reduction of either dietary yeast or sugar can reduce mortality and extend life span, but by an amount that is unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than does sugar. Calorie intake is therefore not the key factor in the reduction of mortality rate by DR in this species.

    Academic Editor: Thomas Kirkwood, University of Newcastle upon Tyne, United Kingdom

    Received: December 20, 2004; Accepted: April 21, 2005; Published: May 31, 2005

    DOI: 10.1371/journal.pbio.0030223

    Copyright: © 2005 Mair et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abbreviations: CI, confidence interval; DR, dietary restriction; SY, sugar yeast

    *To whom correspondence should be addressed. E-mail: [email protected]

    Citation: Mair W, Piper MDW, Partridge L (2005) Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila. PLoS Biol 3(7): e223

    For Long-Lived Flies, It's Calorie Quality, Not Quantity, That Matters
    DOI: 10.1371/journal.pbio.0030237

    Published: May 31, 2005

    Copyright: © 2005 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Citation: (2005) For Long-Lived Flies, It's Calorie Quality, Not Quantity, That Matters. PLoS Biol 3(7): e237

    A Transcriptional Profile of Aging in the Human Kidney
    Graham E. J. Rodwell1, Rebecca Sonu2, Jacob M. Zahn2, James Lund2, Julie Wilhelmy3, Lingli Wang4, Wenzhong Xiao3, Michael Mindrinos3, Emily Crane2, Eran Segal5, Bryan D. Myers1, James D. Brooks6, Ronald W. Davis3,7, John Higgins4, Art B. Owen8, Stuart K. Kim2,7*

    1 Division of Nephrology, Stanford University Medical Center, Stanford, California, United States of America, 2 Department of Developmental Biology, Stanford University Medical Center Stanford, California, United States of America, 3 Department of Biochemistry, Stanford University Medical Center, Stanford, California, United States of America, 4 Department of Pathology, Stanford University Medical Center, Stanford, California, United States of America, 5 Department of Computer Science, Stanford University Medical Center, Stanford, California, United States of America, 6 Department of Urology, Stanford University Medical Center, Stanford, California, United States of America, 7 Department of Genetics, Stanford University Medical Center, Stanford, California, United States of America, 8 Department of Statistics, Stanford University Medical Center, Stanford, California, United States of America,

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

    Academic Editor: Thomas Kirkwood, University of Newcastle upon Tyne

    Received: May 9, 2004; Accepted: October 7, 2004; Published: November 30, 2004

    DOI: 10.1371/journal.pbio.0020427

    Copyright: © 2004 Rodwell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abbreviations: ANOVA, analysis of variance; cRNA, complementary RNA

    *To whom correspondence should be addressed. E-mail: [email protected]

    Citation: Rodwell GEJ, Sonu R, Zahn JM, Lund J, Wilhelmy J, et al. (2004) A Transcriptional Profile of Aging in the Human Kidney. PLoS Biol 2(12): e427

    Nat Med. 2006 Jan;12(1):34-6 Sirt1: a metabolic master switch that modulates lifespan

    Aging Cell. 2006 Feb;5(1):39-50. Related Articles, Links

    Use of microarray biomarkers to identify longevity therapeutics.

    Spindler SR.

    Department of Biochemistry, University of California, Riverside, CA 92521, USA.

    Summary A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemopreventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.

    Science. 2005 Oct 14;310(5746):314-7. Related Articles, Links

    Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS.

    Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO.

    Integrated Laboratories Network, Department of Preclinical Sciences, Luigi Sacco Hospital, Milan University, 20157 Milan, Italy. [email protected]

    Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.
  15. QuikClot

    QuikClot Senior Member 5+ Year Member

    Nov 20, 2005
    I'm happy for you. If you expect the Red Sea to part at those words, you're going to be disappointed.

    Obviously your study of genetics has left you little time to think about issues of rhetoric, meaning, truth and language, for you have a very naive view.

    Of course they do. But there is no suggestion that the aging genes this group is targeting extend life by slowing the metabolism. They work differently. CR has not been found to slow the metabolism.

    So should we all, I'm sure.

    The sci american article is not "second hand"; it was written by one of the scientists doing the primary research. Apparently he does not share your disdain for "lay" sources.

    Incidently, the adjective "lay" is derived from the modern "layman" cf. "laity" which originally meant "not a member of a religious order." Interesting etymology, don't you think?

    You do that. I appriciate your specialized professional take on the subject. I might suggest, with all due respect, that we all have different areas of expertise, and different styles of communicating, and it is always good to leaven our advice with a bit of humility.
  16. jonathon

    jonathon Banned Banned

    Dec 28, 2005
    Quote: "CR has not been found to slow the metabolism."

    You have a lot to learn.

    CR diets reduce amounts of thyroid hormone, which stimulates metabolism. By reducing these hormones, CR helps model organisms to conserve energy by slowing the metabolic rate.

    Caloric restriction causes some organisms to have a slower metabolic rate so they can conserve scarce resources (while some model organisms have increase metabolic rate). When calories are restricted, your metabolism decreases by at least 20-30%. With severe calorie restriction, some studies have shown that resting metabolism can become depressed by as much as 45%!

    An issue people tend to ignore with CR diets is tissue repair. A CR diet slows down the rate of tissue repair and wound repair. A person having surgery that is on a CR diet will take longer to heal and recover from surgery or even trauma. Therefore, medical care cost will go up because of longer hospital stays and more severe damage can occur to tissues when compared to individuals who are on a 2,000 calorie diet.

    CR leads to reduced ability to deal with hypothermia. There is a hypothesis that shows this to be a possible reason why the levels of fat are lesson on a CR diet.

  17. QuikClot

    QuikClot Senior Member 5+ Year Member

    Nov 20, 2005

    This is wrong, per both your sources and mine. Yours:

    Facts, of course, do not speak, but if they could, these facts would be saying "you don't get increases in ATP production and oxydative activity when your metabolism slows. Duh."


  18. 2Bsure

    2Bsure Member 5+ Year Member

    Jan 15, 2006
    It's a pity this is only a virtual forum. If it were real, you two could settle this by whipping 'em out and seeing whose is bigger. Unfortunately, since that is not an option, civility and courtesy will have to suffice.
  19. FutureDocDO

    FutureDocDO 1K Member 10+ Year Member

    Apr 20, 2004
    What media? If you've ever looked into the biomedical aspects of aging you'll see that telomeres do play a role in aging. Genetics class will also mention it. Although there also seems to be a intrinsic clock but no one has been able to tell what it is up to this point.
  20. Moxxie

    Moxxie Rained out 7+ Year Member

    Oct 20, 2005
    Temperate Rainforest
    If I've ever looked into the biomedical aspects of aging? How about that I have four years experience with a molecular biology lab that does aging research and almost got my PhD? I'm not saying that telomeres aren't important - it's just that they are seem to be the first and only thing taught to a lot of students (they were my first introduction to aging research as well). By "media" I suppose that I mean the popular scientific media and most anything CNN/MSN, etc. puts out. Although when you think about it, the general public really gets extremely small exposure to primary research articles.

    Again, I'm not trying to say that telomeres aren't important. I was just trying to point out that there are things OTHER than telomeres that are involved in the aging process. Mitochondria (our little cellular powerhouses) probably play a much bigger, primary role in aging. Shortened telomeres are just one of the biomarkers for aging - oxidatively damaged proteins, DNA and lipids are other good markers. (Excess oxidative stress can cause telomeres to shorten, too - so again, this points to ROS as a more basic cause and shortened telomeres as an effect). Biomarkers like these are used to correlate lifespan and pathological data to help explain the aging process.

    If you want some molecular (non-telomere related) background on aging (including aging and caloric restriction), I would suggest reading these articles (and this is really only skimming - this is getting to be a hot topic in some research circles):

    Van Remmen H, Hamilton ML, Richardson A. "Oxidative damage to DNA and aging." Exerc Sport Sci Rev. 2003 Jul;31(3):149-53.

    Van Remmen H, Richardson A. "Oxidative damage to mitochondria and aging." Exp Gerontol. 2001 Jul;36(7):957-68.

    Ward WF, Qi W, Van Remmen H, Zackert WE, Roberts LJ 2nd, Richardson A. "Effects of age and caloric restriction on lipid peroxidation: measurement of oxidative stress by F2-isoprostane levels." J Gerontol A Biol Sci Med Sci. 2005 Jul;60(7):847-51.

    Phelan JP, Rose MR. "Why dietary restriction substantially increases longevity in animal models but won't in humans." Ageing Res Rev. 2005 Aug;4(3):339-50.

    And finally - this recent article discusses the effects of oxidative stress on telomere length and the subsequent effects on cellular senescence. This article does not, however, think that telomere length is the ultimate answer.

    von Zglinicki T, Martin-Ruiz CM. "Telomeres as biomarkers for ageing and age-related diseases." Curr Mol Med. 2005 Mar;5(2):197-203.

    Have fun!
  21. infiniti

    infiniti Senior Member 5+ Year Member

    Aug 16, 2004
    I agree with everything jonathon has said (except for the personal battle going on with QuikClot). Seeing such phenomenon in mice is certainly progress. We do however have to think about "life" as it relates to humans. Humans are not mice and are certainly not constrained to a cage (at least we, the lucky ones aren't). Science does not exist in a vacuum. Any applicable scientific finding has to take into account human nature. Think of it this way: There are numerous chemical compounds that can kill cancer cells. The trick however is to find the ones that will do so while living the regular cells in tact (or do very little damage to them).
  22. vesper9

    vesper9 Member 7+ Year Member

    Jan 26, 2006
    a laymans/alt-media article on caloric-restriction I recently read, some of you may find interesting?

    Live, Fast, Die Old
  23. Matthewlake

    Matthewlake New Member

    Apr 30, 2006
    I am 21 years old and have been doing Calorie Restriction just after I turned 20. I currently eat around 1700-1800 calories a day and it is really not difficult. One person in here mentioned that you have to put up with a lack of energy, I don't find this to be true at all. I am still able to run just as far and play football for aslong as I want as I always have done. Although I don't exersise all that much anymore because of my reduced caloric intake, I was able to play football (soccer) last week for upto 5-6 hours without any problems.

    as time goes by I will likely cut down to around 1550 calories or so, right now I'm reluctant to go that far as my weight is already low because I started off doing CR at a low BMI (under 20) and don't really want it to go much lower. It will be really interesting to see results from the studies going on in monkeys on CR. I'm confident that there will be some degree of life span extension, but by how much? Can we extrapolate what we see in rodents to higher animals/mammals?

    Some of the short term benifits I've experienced so far are:

    - All Allergies supressed or dissapeared
    - Don't seem to get sick anymore with colds/flu etc...
    - Need less sleep

    As I am still young I doubt that I will need to carry on with CR in the future, as CR mimmetics will likely be created or reversal of age associated diseases through various methods being developed and tested today.
  24. BiOGoly

    BiOGoly 10+ Year Member

    Jun 12, 2003
    Portland Oregon
    Unless you are Paul Bunyan I don't think 1800 kcal a day is enough caloric restriction to slow the aging process, at least in the same way that current research suggests it occurs in mice. If the same kind of caloric restriction that mice require to achieve increase longevity applied to humans, you'd have to consume 60% of a normal caloric intake...for the average person this would be about <1500 calories.

    The most interesting thing I've read about these CR studies is that not only do the mice display increase longevity, but they experience significantly fewer cancers and appear to be much more vigourous in "old age". Fascinating stuff!

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