Dean Pomerleau Posted January 28, 2016 Report Share Posted January 28, 2016 In this Quora Q&A, Aubrey share's his perspective on calorie restriction in humans with a 20 year-old thinking about starting CR. Its really quite a sensible answer, and he mentions the CR Society! Question: If I am in my early twenties, should I bother with caloric restriction or should I sort of rely on medicine to advance enough by the time I would be old enough for it to make a difference? (Personally, I maintain an active lifestyle including regular strength training so I actually eat *a lot*.) Aubrey de Grey Answer: There is a wide spectrum of opinion within the academic biogerontology community concerning the likely benefit of CR in humans. I personally am rather pessimistic, for reasons that I set out several years ago here: http://www.ncbi.nlm.nih.gov/pubmed?term=15711074 But to answer your question directly: interventions that bring aging under genuine medical control, actually rejuvenating people rather than just slowing aging down, are still too far off for us to have any idea of exactly how far. So, no matter how young or old you are today, anything you can do to stay alive and healthy for as long as possible increases your chances of being around when those therapies do arrive. If you find it not too stressful to do CR, and you do it knowledgeably (according to the recommendations of the CR Society, for example), it probably won't hasten your aging - and if I'm wrong in my pessimism above, it might be worth doing. --Dean Link to comment Share on other sites More sharing options...
Sthira Posted January 28, 2016 Report Share Posted January 28, 2016 Total agreement. CR might hasten some people's aging, and it might slow someone else's aging? How are we supposed to know who we are, and into which category we fit? Blood draws? Feeling? I feel good on CR, I feel bad on CR, which is it? Sometimes feeling good is unhealthy and feeling bad is healthy. We don't have many choices, do we, and yet paradoxically we probably have more choices, more insight into what it means to be healthy than any of our ancestors had in recorded history. Meanwhile, aging continues unabated. Slow the pace or speed the pace -- we've no damn idea. Link to comment Share on other sites More sharing options...
gracezw Posted January 28, 2016 Report Share Posted January 28, 2016 In this Quora Q&A, Aubrey share's his perspective on calorie restriction in humans with a 20 year-old thinking about starting CR. Aubrey de Grey Answer: There is a wide spectrum of opinion within the academic biogerontology community concerning the likely benefit of CR in humans. ... interventions that bring aging under genuine medical control, actually rejuvenating people rather than just slowing aging down, are still too far off for us to have any idea of exactly how far. So, no matter how young or old you are today, anything you can do to stay alive and healthy for as long as possible increases your chances of being around when those therapies do arrive. If you find it not too stressful to do CR, and you do it knowledgeably (according to the recommendations of the CR Society, for example), it probably won't hasten your aging - and if I'm wrong in my pessimism above, it might be worth doing. I am confused. Does this mean that de Grey regrets investing his family money into SENS? Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 28, 2016 Author Report Share Posted January 28, 2016 Huh? Grace, why would you get that interpretation from his answer to this question? I interpret his response to mean that he is realistic in his assessment that true anti-aging therapies for people are still a long way off, despite the progress they are making at SENS and elsewhere. So people should do what they can to slow the aging process using existing strategies like a good diet, healthy lifestyle, and possibly CR if you can tolerate it, despite their limited effectiveness. The pessimism he's referring that I've bolded at the end is not pessimism about anti-aging research in general - but rather about the likely (lack of) effectiveness of CR for extending human lifespan, if that what was confusing you. --Dean Link to comment Share on other sites More sharing options...
gracezw Posted January 29, 2016 Report Share Posted January 29, 2016 Dean, thank you for your explanations. That really helps. My next two questions are: 1) Could you explain more about the “limited effectiveness” of “good diet, healthy lifestyle and CR”? For example, how many more years does an average CR practitioner expect to live than what he would otherwise? Is it realistic to expect him to live up to 120 years? 2) I got it that anti-aging research in general has made a lot of progress. In terms of extending human lifespan, the limited effectiveness of what is de Grey pessimistic about -- CR, medical interventions/therapies, or both? Also am I supposed to get email notifications when someone publishes a new post or thread? I haven’t gotten any yet. Link to comment Share on other sites More sharing options...
Sthira Posted January 29, 2016 Report Share Posted January 29, 2016 Hi Grace, I'm not Dean, of course, but my take is that a good diet, a healthy lifestyle, and CR won't extend our lives too much. Even if we lived our lives perfectly from day one infancy -- ate all the right stuff, exersized the perfect amount, slept beautifully every night for the correct amount of time, even if we lived lives of absolute current-thinking healthy flawlessness, we're still aging right on schedule. The pessimism, I reckon, extends not just from potentialities of CR, but to anything, everything we do that we call healthy living. We may live longer, happier lives with less sickness and disease if we treat our bodies well. But these healthy habits won't stop the damage caused by aging process. They may help us live less diseased lives, but eventually we'll be robbed of all our good habits, and down we go. To stop the aging process requires specific repair treatments, some of which he's outlined, and none of which appear anywhere close to being developed. Yet. Stay tuned and donate, we're advised, cures for repairing the body, then slowing aging, stopping aging, reversing aging may be coming our way. When? They need more money to speed the process. But they're confident the work will be done -- but maybe no time soon. I don't think anyone knows how many more years an "average CR practitioner" can expect to live even if the discipline is practiced perfectly. Is there an average CR practitioner? We're all indie snowflakes, of course, and CR might expand one person's healthy life, yet contract another's. But de Grey seems to be saying that at best CR may only add a few years of extra life. And maybe not even that. Has "anti-aging made a lot of progress" as you write? I'm not arguing meaninglessly, I'm just curious what progress has been made. I see great potential ahead; but nothing appears before us now to repair the damages. The closest I've seen in extending LS in mice was Baati's Carbon 60 in olive oil toxicity study, where mice lifespans were dramatically extended. But that study has mostly been ignored until very recently, and hasn't been replicated. I don't receive email indications about posts here, either, fwiw. Link to comment Share on other sites More sharing options...
gracezw Posted January 29, 2016 Report Share Posted January 29, 2016 Sthira, I am surprised to hear you say that CR won’t extend our lives too much. Dean posted elsewhere comparing vegetarians’ lifespan with meat eaters’. The difference was like, 12-14 years! Those are a lot of years and motivating! I thought that CR would either do the same or even better. Is living to be 100 or 120 just wishful thinking? You said, “CR might expand one person's healthy life, yet contract another's.” I thought CR would generally expend most or all practitioners’ healthy lives. If not, what do they practice CR for? You asked, “Has "anti-aging made a lot of progress" as you write?” I am in the middle of Brian’s book and Paul & Meredith’s book. I have been reading on this forum for a coupe of weeks. My general impression is that a lot of progress has been made. Thanks for letting me know. I feel better that I am not the only person who does not receive email notifications. J Link to comment Share on other sites More sharing options...
gracezw Posted January 29, 2016 Report Share Posted January 29, 2016 I was hoping that CR would help us live both longer and less diseased lives. I would be happy with 8-10 years longer. Link to comment Share on other sites More sharing options...
Zeta Posted January 29, 2016 Report Share Posted January 29, 2016 Grace, 8-10 years would be great for me, as well! Heck, CR would be worth it if I got 2 or 3 extra years! About the email notifications: a few of us have had problems with that. Go into your settings and try setting everything to maximum notification criteria, and then cut back once you see it's working. That's what I did. Zeta. Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 29, 2016 Author Report Share Posted January 29, 2016 Grace, Thanks for sparking some fine discussion! You pose some really good questions. FWIW, I agree with both Sthira's and Khurram's responses. In particular, I agree with: Sthira when he says (summary) that CR may or may not slow aging appreciably in people (more on that below), and interventions that really do slow, or especially, reverse the damage that accumulates with aging, are still at least a decade (and perhaps several decades) away from human availability. Khurram when he says there are several of us who practice CR (or in my case, a bastardized version of CR that some would deny is anything close to the real thing) for its other benefits many of which are psychological but some physical as well. But this is not to deny (as Khurram points out) that CR can mess with you head too, so buyer beware... (BTW Khurram - thanks for the link to the Minnesota Starvation Study video. Ancel Keyes was an amazing researcher, and those men were heroic as well) On to your two specific questions: 1) Could you explain more about the “limited effectiveness” of “good diet, healthy lifestyle and CR”? For example, how many more years does an average CR practitioner expect to live than what he would otherwise? Is it realistic to expect him to live up to 120 years? Perhaps Brian can chime in to share how his views have (or haven't) changed wrt the longevity benefits of CR since he and Lisa Walford wrote The Longevity Diet. But I think it's fair to say that in the past decade or so, the optimism that CR could extend human lifespan dramatically, perhaps to 120 years for the average person who did it seriously for their entire adult life, has been tempered substantially. I think this is largely a result of the rather disappointing results from the recently published studies of lifelong CR in monkeys conducted at the University of Wisconsin [1] and the National Institute on Aging (NIA) [2]. We've discussed these extensively elsewhere, and Michael Rae went into massive detail in his analysis of the two primate studies, so I will only summarize the results and their implications as I see them for people. In short, the Wisconsin researchers fed their monkeys a fairly crappy diet in either nearly ad lib amounts (the control group), or 30% less than ad lib (the CR group). The Wisconsin control group got obese, while the CR group remained lean. See this cued-up video for a visual comparison of the two groups of Wisconsin monkeys. The obese control group, which you might equate with people eating a standard American diet in too large a quantity, died relatively young, while the CR group suffered fewer diseases and lived longer. So chalk one up for CR! That was the good news... The not-so-good (but perhaps not that bad, see below) news came from the NIA monkey CR study. There, the researchers fed both groups of monkeys a healthier, higher quality diet than the Wisconsin monkeys got. Plus they limited the amount of food the control group got so they didn't get really fat like the Wisconsin control monkeys did. The NIA controls were heavier than the CR group (who ate 30% less of the same healthy food), but they were within the healthy weight range for monkeys. So this was considered by many to be a fairer comparison for gauging the benefits of CR proper relative to a healthy-but-not-especially-calorie-restricted diet. And the results were kinda disappointing. While there were some qualifications worth considering (see Michael's mega post for details), the bottom line was that the NIA CR monkeys didn't live longer than the NIA control group. So that was disappointing for those who believed CR would provide dramatic longevity benefits. But on the bright side, both groups of monkeys in the NIA experiment lived substantially longer than previous studies of monkeys in captivity. This, coupled with recent similar evidence from CR experiments in rodents and dogs, suggests that much (most?) of the health and longevity benefit of CR in mammals may be captured by eating a healthy diet and avoiding obesity. So what does this mean exactly for humans? Putting the animal results together with the data from the clean-living Adventists, I think a fair interpretation is that by eating a healthy diet in modest amounts to stay slim throughout adulthood and avoiding unhealthy practices like smoking, the average person might expect to live into their late 80s or perhaps early 90s (ignoring other life extension breakthroughs between now and then that might tack on extra years). Serious CR on top of a healthy diet and lifestyle is unlikely to give you many additional years - optimistically maybe 5-8 extra years, but realistically probably less than that. Unfortunately, the former optimistic projections of living to 120 as a result of CR appear pretty unrealistic now, based on the latest animal data... 2) I got it that anti-aging research in general has made a lot of progress. In terms of extending human lifespan, the limited effectiveness of what is de Grey pessimistic about -- CR, medical interventions/therapies, or both? Aubrey is definitely pessimistic about CR - he thinks CR will likely only provide humans a couple extra years at best. He's very optimistic about anti-aging therapies in the long-run, but he acknowledges that such interventions are not here yet, and will likely take several decades before they are available for the general public. Hence he suggests doing whatever we can to maintain health and slow the aging process through a healthy diet and lifestyle, and (perhaps) CR if you can tolerate it. --Dean ----------- [1] Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4. PubMed PMID: 19590001; PubMed Central PMCID: PMC2812811. [2] Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. [Epub ahead of print] PubMed PMID: 22932268. Link to comment Share on other sites More sharing options...
Sthira Posted January 30, 2016 Report Share Posted January 30, 2016 Thank you, Dean, for your usual cheerful and helpful post. CR seems to extend lifespan in almost every species where it's been studied. For this reason alone CR is certainly worth experimenting with on your own body. If I could do it, I would. And I envy those who like Khurram can do it, and thrive; but I may be too much of a hyperactive spaz to make it fly for me. I love moving my body around in space with ease, and for me life on +/-20% CR was a life of huff and puff and whoopsie boy am I dizzy, mind if I just sit down here and rest? I'm 20-pounds heavier now at 6'2" 150 pounds, and when my low CR fun times dipped to 123 people around me thought I had an eating disorder or cancer. Fasting works well for me now -- single day, three-days, five-days, and seven. But fasting may not offer the same benefits as it might in combo with CR, and extended fasting may not be so great for a beating human heart. Grace, you should definitely at least play and experiment for yourself with CR, your body may love it, it's unlikely to cause damage other than hunger, which is mostly psychological, and it may be fun and interesting to feel as though you're doing something healthy for yourself. You may indeed be one of the lucky people to acheive drastic lifespan extension -- someone on CR probably will acheive drastic life extension since life is strange like that. The bummer is that no one seems to know. That's gonna change, though, many CR practitioners are older in chronological years, so coming up we'll perhaps see who's still rocking the dance floor at 135. Link to comment Share on other sites More sharing options...
gracezw Posted January 30, 2016 Report Share Posted January 30, 2016 Dean, I have another another related question. What diseases would a NIA CR Monkey person prevent or reduce comparing with what a NIA Control Monkey person would? Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 30, 2016 Author Report Share Posted January 30, 2016 Sthira, ... CR is certainly worth experimenting with on your own body. If I could do it, I would. ... I'm 20-pounds heavier now at 6'2" 150 pounds... At 6'2" and 150lbs, your BMI is 19.3. That's the sweet spot for CR according to many, and exactly where most CR practitioners fell in our recent CR survey. What makes you say you're not doing it anymore, just because you've gained some weight? --Dean Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 30, 2016 Author Report Share Posted January 30, 2016 Admin Note: I've taken two posts from this thread, by Khurram and Grace, focused on CR Psychology, and created a new thread for them, since they touch on a very important topic that deserves its own thread. Please follow this link to continue reading and contributing to that discussion. I'll be contributing to it myself shortly. --Dean Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 30, 2016 Author Report Share Posted January 30, 2016 Grace, Dean, I have another another related question. What diseases would a NIA CR Monkey person prevent or reduce comparing with what a NIA Control Monkey person would? From the full text of study [1] of the NIA CR monkey study, the young-onset CR monkeys enjoyed better immune function, better oral health, less inflammation and reduce rates of cancer. Unfortunately, when CR was begun in adult monkeys these benefits were not observed. Again, if you or anyone is really interested in the CR monkey results, I can't recommend reading Michael's review highly enough. --Dean --------- [1] Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. [Epub ahead of print] PubMed PMID: 22932268. Link to comment Share on other sites More sharing options...
Saul Posted January 30, 2016 Report Share Posted January 30, 2016 Hi ALL! Remember, the two monkey studies are just two studies -- the many deductions that many have projected are definitely unwarranted -- the correct answer is "insufficient data for any semi-definitive conclusion". The truth is, that we don't really know how much benefit we can expect from CR -- we are the guinea pigs; our lifespan and healthspan will give more data. That said, there IS significant evidence that CR appears to extend healthspan -- and we don't know whether CR in humans will extend lifespan 2 years, 5 years or more (or less). But you're definitely ahead in likely extending your healthspan if you practice CRAN, do aerobic exercise (like Claudet) -- my guess, more than just "moderate" AEROBIC exercise -- and lead a calm (not stressful) lifestyle (perhaps practicing Meditation). -- Saul Link to comment Share on other sites More sharing options...
Michael R Posted January 31, 2016 Report Share Posted January 31, 2016 There's to which I'd like to respond in this thread and elsewhere, but I do feel compelled to jump in on this point right away: Grace, Dean, I have another another related question. What diseases would a NIA CR Monkey person prevent or reduce comparing with what a NIA Control Monkey person would? From the full text of study [1] of the NIA CR monkey study, the young-onset CR monkeys enjoyed better immune function, better oral health, less inflammation and reduce rates of cancer. Unfortunately, when CR was begun in adult monkeys these benefits were not observed. No, this isn't accurate. The "young-onset" group as delineated in (1) includes the adult-onset animals: the contrast is not between young-onset animals (meaning juveniles) enjoying these health benefits (and diabetes, and possibly a couple of other better outcomes) while adult animals not, but between young-onset animals (a plurality of adults, along with juveniles and adolescents) while old-onset animals did not. [1] Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. [Epub ahead of print] PubMed PMID: 22932268. Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted January 31, 2016 Author Report Share Posted January 31, 2016 Michael, Thanks for that important clarification / correction to my portrayal of the NIA results. Would you mind spelling out what human-equivalent ages best correspond to the various ages at which CR was initiated in the NIA monkeys? Most importantly, at what age (in humans years) was CR initiated in the old-onset animals, who didn't benefit on (even) the health markers? Thanks, --Dean Link to comment Share on other sites More sharing options...
Michael R Posted January 31, 2016 Report Share Posted January 31, 2016 Would you mind spelling out what human-equivalent ages best correspond to the various ages at which CR was initiated in the NIA monkeys? Most importantly, at what age (in humans years) was CR initiated in the old-onset animals, who didn't benefit on (even) the health markers? I don't think anyone can answer that quantitatively, unfortunately: interspecies "human-years" are a somewhat iffy comparison in general, and we can only do a pretty good job of mice and domestic dogs because we have long and extensive records and (in the case of mice) a lot of well-controlled data. We don't have the equivalent for nonhuman primates, and what records we do have for rhesus monkeys may all have to be thrown out as worthless if indeed the NIA controls are the first proper control animals in the history of the species (as is suggested by the fact that "50% survival for the females is 27.8 years and 35.4 years for the males, exceeding the ≈27 year median lifespan previously reported for monkeys in captivity " and the suggestion of an historical record for max LS may emerge as well). . I think we have to trust the reasonably clear qualitative designations of "adult" and "old." "Juvenile" and "adolescent" are fairly clearly biological categories, but even so putting calendar years on them is fraught, as humans are a neotonous primate with a greatly-extended childhood. Link to comment Share on other sites More sharing options...
Sthira Posted January 31, 2016 Report Share Posted January 31, 2016 Since these were macaques isolated in separate prison cages, maybe the ages of the jailed macaques on CR should be guessed up against ages of jailed, isolated humans on CR? Link to comment Share on other sites More sharing options...
BrianMDelaney Posted January 31, 2016 Report Share Posted January 31, 2016 Perhaps Brian can chime in to share how his views have (or haven't) changed wrt the longevity benefits of CR since he and Lisa Walford wrote The Longevity Diet. But I think it's fair to say that in the past decade or so, the optimism that CR could extend human lifespan dramatically, perhaps to 120 years for the average person who did it seriously for their entire adult life, has been tempered substantially. I'm still optimistic about CR for humans, but I increasingly think of it as a way to stave off disease for genetically typical humans. Starting a very rigorous CR program in early adulthood could prevent or push back heart disease or type 2 diabetes so much that typical humans would likely get a tremendous increase in length of life – 10-20 years or in some cases much more, if they started in early adulthood and followed it consistently and rigorously. That, as opposed to thinking of it as a way to slow aging per se dramatically. (The difference between those two views is, of course, not easy to maintain, given the complexities of defining aging itself.) In other words, normal "strains" could benefit tremendously from CR, and certain sickly strains could benefit even more, but about the longevous strains (which are pretty rare), I'm less certain. We have no evidence of a 130-year-old Okinawan. Not sure how much that matters: As I've said before, I think one could make the case that a reasonable definition of the maximum lifespan of humans (which would be precisely the figure that includes longevous strains) is something like 95 or 100 years. I'm saying, obviously, that people living longer than that – all of them – have actually been on mild CR for much of their lives. In any event, most of us start CR later in life, and most of us don't do it extremely rigorously or consistently. (I certainly haven't.) I still think anyone interested in living a long life should consider CR, esp. those who have a strong genetic predisposition towards the classic diseases of aging (cardio-vasc. disease, type 2 diabetes, dementia). - Brian Link to comment Share on other sites More sharing options...
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