31 replies to this topic

[Brett Black]

All the evidence from rodents(http://www.imminst.o...50) shows that even the most severe(and lifespan extending) levels of adult-onset caloric restriction will add a maximum of 10%-20% to total lifespan(about 8-16 human years.) That sounds ok, if not brilliant, but nowhere near the levels of lifespan increase that occurs with childhood-onset CR(that also happens to stunt growth by about 50%) which are often the figures regularly touted.

However, before we get too excited over these results, let's extrapolate the adult-onset rodent experiments and results to adult humans(after all, that is the basis upon which calorically-restricted lifespan extension currently rests):

To accurately emulate the experiments in rodents, an adult human would need to cut approximately 50% of the calories from their normal diet.

Let's assume we start with a well-padded young adult male of 75kg(165lbs) weight and 24 BMI. He is absolutely sedentary, which is a positive for CR, since it allows him to minimize his calorie intake.

Cutting his calories by 50%(even if done very gradually) would eventually lead to him weighing just half(or even less) of his initial weight.

After making his transition to his new 50% reduced diet, his final weight would be just 32kg(71lbs) and he would have a BMI of about 10.

He would make the worst concentration-camp skeletal bodies look morbidly obese in comparison.

Put simply, no one could survive at such a weight and calorie restriction level.

Since no human could survive such extreme caloric restriction, we're going to have to decrease the amount of caloric restriction. Unfortunately, along with decreasing the severity of caloric restriction, we're also going to see a related decrease in life extending effect. A 10%-20% increase in lifespan is just not going to be realistic.

Still, let's push the caloric restriction really far. Let's push it to the absolute extreme levels of human tolerability. Let's aim for a BMI of 15. People have lived at this weight, but they look like skeletons, literally. This is around the level of body weight of the worst anorexic sufferers you've ever seen.

Let's assume that this young man(despite the major impacts on strength, energy, social perception, hunger etc etc) manages a BMI of 15. At this BMI he would weigh about 45kg(99lbs.) Now let's just imagine that he somehow avoids any other (and potentially unknown)health complications associated with being a living skeleton. What level of caloric restriction would he be able to practice at this extreme?

Believe it or not, he would only be able to cut around 20% of calories from his diet. This level of caloric restriction, which equates to about the most extreme caloric restriction possible in an adult human, is still less than half of that carried out in the rodent experiments.

So what type of lifespan extension can he expect from such extreme food restriction? The rodent studies show an approximately linear relationships between calorie restriction and lifespan extension. Since he's "only" on 20% calorie reduction, he can expect a maximum of 5%-10% life extension, or about 4-8 years.

In summary, the evidence at this point shows that the costs far outweigh the benefits of life extension via caloric restriction. Fifty to sixty years of living as a hungry weak pathetic sedentary skeleton for 4-8 years of extra life during the "declining last years" of life.

Edited by Brett Black, 10 July 2010 - 06:17 AM.

[Mind]

Some of the more severe CRONies do look skeleton-ish. However, most are just very thin and they seem to maintain strength and vitality, so I don't think weak is an accurate term. Rodent studies show that they maintain their muscle strength into old age much better than controls. CRONies also claim that hunger sensations are not very bad. I guess if the down-sides of CR are non-issue for some people, then 4-8 would be a pretty nice bargain.

[Brett Black]

Some of the more severe CRONies do look skeleton-ish. However, most are just very thin and they seem to maintain strength and vitality, so I don't think weak is an accurate term.

The "weak" comment of mine was specifically in regard to people practicing the severest levels of CR. How many of these "very thin" but still maintaining "strength and vitality" CRONies that you've seen are young males with a BMI of 15(or less), for instance?

Rodent studies show that they maintain their muscle strength into old age much better than controls.

Calculations(e.g. Mifflin RMR) show that an adult human starting from a "normal" BMI range, and then put on the same caloric restriction level as the most life-extending adult-onsent rodent CR studies(~50%), would simply die(ie have no muscle strength.)

CRONies also claim that hunger sensations are not very bad. I guess if the down-sides of CR are non-issue for some people, then 4-8 would be a pretty nice bargain.

The 4-8 years of extra life would only be for CRONies who practiced close to the most extreme level of caloric restriction humanly possible. Those who practice less severe CR will(if the rodent data holds true) see even less than the 4-8 years addition to lifespan.

Edited by Brett Black, 10 July 2010 - 01:59 PM.

[Luna]

Well CR isn't the way to live forever anyways.

[Michael]

All the evidence from rodents(http://www.imminst.o...50) shows that even the most severe(and lifespan extending) levels of adult-onset caloric restriction will add a maximum of 10%-20% to total lifespan(about 8-16 human years.)

Where did you get these numbers? the link you give as "all the evidence" doesn't actually cite any evidence to that effect, let alone "all the evidence." In (1), 25% CR initiated at age 12 mo (human ~33 y) led to a ~16% increase. This is not "the most severe" CR. However, I do agree (although not because of the rest of your analysis, which among other things depends too directly on BMI) that it's unlikely that free-living humans will actually practice more severe CR than this, so let's go with that for the moment:

In summary, the evidence at this point shows that the costs far outweigh the benefits of life extension via caloric restriction. Fifty to sixty years of living as a hungry weak pathetic sedentary skeleton for 4-8 years of extra life during the "declining last years" of life.

First, as Mind says:

Some of the more severe CRONies do look skeleton-ish. However, most are just very thin and they seem to maintain strength and vitality, so I don't think weak is an accurate term.

The "weak" comment of mine was specifically in regard to people practicing the severest levels of CR. How many of these "very thin" but still maintaining "strength and vitality" CRONies that you've seen are young males with a BMI of 15(or less), for instance?

Lots of women . I don't actually know of any male CR practitioners with BMIs ≤ 15. I'm above that, and am pretty damned skinny -- but I certainly have "strength and vitality." Again, as Mind also says

Rodent studies show that they maintain their muscle strength into old age much better than controls.

Calculations(e.g. Mifflin RMR) show that an adult human starting from a "normal" BMI range, and then put on the same caloric restriction level as the most life-extending adult-onsent rodent CR studies(~50%), would simply die(ie have no muscle strength.)

Note: I am not dead . Again, one certainly does not (on a linear extrapolation) have to go on 50% CR to get the extension of youthful life under discussion (10-20%). The Minnesota Starvation Experiment participants may possibly have been on 50% CR, though I have doubts; they in any case did not die during the study and showed no signs of doing so, despite being malnourished despite Keys' intentions.

In any case, you haven't actually addressed his point, which is that the biological aging process will strip away the strength in an aging body in any case; those smaller muscles work better in CR rodents and primates, and they also keep the reflexes and muscle control to actually use them.

Now let me finally circle back to that "declining last years of life" bit. Of course, this either misses the point, or is a petitio principii with a false premise: the whole point of the exercise is to expand the period of youthful health and vigor. This is exactly the mental trap of all those people who, when you talk to them about life extension, say "well, why would you want to get that old?" The point is not to get old -- or at the least, to delay the degenerative process for as long as possible. In CR animals, the "declining last years of life" are, at worst, no longer or worse than in AL animals: they stay youthful and vigorous longer, and then spend at worst the same amount of time in decline -- just later in life. And if the multiple reports of large numbers of dead CR mice with bodies free of gross pathology mean what a simplistic interpretation suggests it might, may additionally make the "declining last years of life" themselves much more comfortable, which would be a bonus.

One more thing on that:

Well CR isn't the way to live forever anyways.

Of course it is . Oh, OK, seriously: of course, no one expects that CR will lead to actual immortality. As Mind says, successful CR practitioners have mostly adapted to the side effects they may or may not encounter, and consider them to be a good tradeoff for the expected gains -- and the present ones. Stripping away qualifiers and being a salesman, we're never sick; it banishes migraines, inflammatory disorders, and anxiety; it calms the mind and grants rational clarity; it fills the body with an incomparable global sense of health that -- in my experience and that of everyone on hard CR that I've asked -- is not only delicious and wonderful, but qualitatively and "quantitatively" incomparable to any ad lib state. Also, while (again) I'm inclined to agree with your ballpark estimate of how much the gain in healthy lifespan is likely to be, I not only still consider that to be a pretty good deal in but also do factor in the good chance that the extra years -- and especially, the extra healthy, robust years, not only at the end but in midlife and early seniority -- will increase the odds that we will not only be alive, but in sufficiently physiologically robust condition to endure the rigors of the first, crude, experimental panel of regenerative engineering therapies to arrest and reverse aging.

Aging and death are horrors against which I will not stand idle, nor chase the latest snake oil, nor allow minor inconveniences and discomforts to dissuade me from engaging in the only intervention with a scientific case to retard the process in humans at the present time. You pays your money and you takes your picks.

Reference
1. Pugh TD, Oberley TD, Weindruch R. Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. Cancer Res. 1999 Apr 1;59(7):1642-8. PMID: 10197641 [PubMed - indexed for MEDLINE]

Edited by Michael, 10 July 2010 - 03:14 PM.

[Brett Black]

[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']
[quote name='Brett Black' date='10 July 2010 - 01:29 AM' timestamp='1278739752' post='418081']All the evidence from rodents(http://www.imminst.o...50) shows that even the most severe(and lifespan extending) levels of adult-onset caloric restriction will add a maximum of 10%-20% to total lifespan(about 8-16 human years.) [/quote]
Where did you get these numbers? the link you give as "all the evidence" doesn't actually cite any evidence to that effect, let alone "all the evidence."[/quote]

Sorry, I see the problem, it's a technical problem - I attempted to link to the fourth post in that thread, but it seems like the link is only jumping to the first post. Have a look at the fourth post in that thread, here's an excerpt from it:

[quote]“Control mice (N = 68) were fed enough of diet 1 (~160 kcal/ week) to maintain their initial body weights throughout much of their subsequent life-spans. The mice to be restricted in their diet (N = 67) received diet 2 (~115 kcal/week) for 1 month and diet 3 (-90 kcal/week) thereafter”[/quote]

So, ~45% adult-onset caloric restriction, and the results:


[quote]"The mean and maximum life-spans of these animals increased by an average of 10 to 20 percent"[/quote]

These numbers are similar across all the adult-onset rodent studies that I'm aware of. Do you have any data that shows a significant departure?



[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']In (1), 25% CR initiated at age 12 mo (human ~33 y) led to a ~16% increase. This is not "the most severe" CR. However, I do agree (although not because of the rest of your analysis, which among other things depends too directly on BMI)that it's unlikely that free-living humans will actually practice more severe CR than this, so let's go with that for the moment:[/quote]

I think using the conventionally "healthy" BMI range of 18-25 gives a wide enough margin to be entirely reasonable for defining the limits of the so-called ad libitum "set point" for the great majority of humans.

For a human adult to actually be capable of sustaining a 50% calorie restriction(relative to their initial set point) would likely require defining the set point to be in the morbidly obese ~40+ BMI range. That is surely unreasonable. And, if you were to allow the set point to be placed in this morbidly obese range, then that could simultaneously be interpreted as redefining every human with a normal BMI as being a CR practitioner by default.

[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']
[quote name='Brett Black' date='10 July 2010 - 09:31 AM' timestamp='1278768702' post='418132']How many of these "very thin" but still maintaining "strength and vitality" CRONies that you've seen are young males with a BMI of 15(or less), for instance? [/quote]
Lots of women . I don't actually know of any male CR practitioners with BMIs = 15. I'm above that, and am pretty damned skinny -- but I certainly have "strength and vitality."[/quote]

Everything you've said there lacks relevance to my points:

1. Male? No.
2. BMI of 15 or less? No.
3. Male, BMI of 15 or less and still maintaining strength and vitality? No.

[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']
[quote name='Brett Black' date='10 July 2010 - 09:31 AM' timestamp='1278768702' post='418132']Calculations(e.g. Mifflin RMR) show that an adult human starting from a "normal" BMI range, and then put on the same caloric restriction level as the most life-extending adult-onsent rodent CR studies(~50%), would simply die(ie have no muscle strength.)[/quote]

Note: I am not dead [/quote]

Have you been on "the same caloric restriction level as the most life-extending adult-onsent rodent CR studies(~50%)" that I was clearly referring to? If not, your comment is irrelevant.


[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']
Again, one certainly does not (on a linear extrapolation) have to go on 50% CR to get the extension of youthful life under discussion (10-20%).[/quote]

Again? Irrelevant - my posts so far(and the thrust of this thread, which I started) haven't been dealing with extending "youthful life", but simply extending plain "lifespan."


[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']The Minnesota Starvation Experiment participants may possibly have been on 50% CR, though I have doubts; they in any case did not die during the study and showed no signs of doing so, despite being malnourished despite Keys' intentions.[/quote]

I have been talking about extending normal lifespan, the Minnesota Starvation Experiment had nothing whatsoever to do with extending normal lifespan - it was a study into short-term starvation(it only lasted about a year) and subsequent rehabilitation from the ravages of starvation. Again, irrelevant.


[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']In any case, you haven't actually addressed his point, which is that the biological aging process will strip away the strength in an aging body in any case; those smaller muscles work better in CR rodents and primates, and they also keep the reflexes and muscle control to actually use them.[/quote]

His abrupt unannounced switch from rodents to humans leads me to assume that he was haphazardly and probably unnknowingly mixing human and rodent studies. Yes, studies show that CR rodents can have higher grip strength tests in old age compared to ad-lib controls. Reiterating however, big HOWEVER, humans subjected to the same levels of caloric restriction will likely die in short order, so any supposed retention of muscle strength is a moot point as regards humans on the same CR regime.


[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']Now let me finally circle back to that "declining last years of life" bit. Of course, this either misses the point, or is a petitio principii with a false premise: the whole point of the exercise is to expand the period of youthful health and vigor.[/quote]

My central premise has been stated unambiguously - "Severest CR will add just 4-8 years to human life" - and my arguments have been consistent with it. There may be a stronger argument for an expanded period of health in humans if the CR is more moderate.


[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']This is exactly the mental trap of all those people who, when you talk to them about life extension, say "well, why would you want to get that old?" The point is not to get old -- or at the least, to delay the degenerative process for as long as possible. In CR animals, the "declining last years of life" are, at worst, no longer or worse than in AL animals: they stay youthful and vigorous longer, and then spend at worst the same amount of time in decline -- just later in life. And if the multiple reports of large numbers of dead CR mice with bodies free of gross pathology mean what a simplistic interpretation suggests it might, may additionally make the "declining last years of life" themselves much more comfortable, which would be a bonus. [/quote]

But, as I've shown, directly extrapolating the levels of CR that appear to give the best life and health result to rodents, is very likely deadly to humans. Reducing the CR in humans to even the highest tolerable levels and extrapolating those levels of CR studies in rodent experiments leads to the conclusion that the life extension effects will be relatively negligible in humans.

[quote name='Michael' date='10 July 2010 - 03:09 PM' timestamp='1278774565' post='418151']Stripping away qualifiers and being a salesman, we're never sick; it banishes migraines, inflammatory disorders, and anxiety; it calms the mind and grants rational clarity; it fills the body with an incomparable global sense of health that -- in my experience and that of everyone on hard CR that I've asked -- is not only delicious and wonderful, but qualitatively and "quantitatively" incomparable to any ad lib state.[/quote]

I do find this very interesting, however, without rigorous scientific evidence I don't see how it can be much more than a collection of highly subjective anecdotes.

<continued in next post.....>

Edited by Brett Black, 11 July 2010 - 05:07 AM.

[Brett Black]

<continuing......>

Also, while (again) I'm inclined to agree with your ballpark estimate of how much the gain in healthy lifespan is likely to be,

Ok, I want to be very clear about this point, because from what I've seen, you are considered a notable figure in online CR circles, and a lot of people seem to pay quite a bit of attention to what you say and believe. So:

You agree, that based on extrapolation from current adult onset caloric restriction studies in rodents, that about a 5% to 10% increase in lifespan is what the average person could expect if they practiced severe caloric restriction? Yes?

I not only still consider that to be a pretty good deal in but also do factor in the good chance that the extra years -- and especially, the extra healthy, robust years, not only at the end but in midlife and early seniority -- will increase the odds that we will not only be alive, but in sufficiently physiologically robust condition to endure the rigors of the first, crude, experimental panel of regenerative engineering therapies to arrest and reverse aging.

I think that when put into this context, your basic argument for CR is considerably stronger. I do question however, if CR would be any more beneficial than a conventional, but intelligently planned active lifestyle and diet(basically adhering to the best advice of mainstream health authorities.)

According to my personal preferences, a lifetime filled with enjoyable physical activity and a well-designed and pleasurable diet would trump years of severe caloric restriction, and I think the evidence(of which there is mountains more than CR) is that it may be approximately as beneficial to lifespan and healthspan as CR.

Aging and death are horrors against which I will not stand idle, nor chase the latest snake oil, nor allow minor inconveniences and discomforts to dissuade me from engaging in the only intervention with a scientific case to retard the process in humans at the present time. You pays your money and you takes your picks.

While I do question your choice of method, I admire your ultimate goal, your determination and your single-mindedness.


---


(Resting Metabolic Rate and caloric intake/expenditure calculations["Mifflin RMR" equations] used can be accessed here:)
http://www.scientifi...alth/cron1.html


(Here as some of the studies used to calculate the expected increase in lifespan for humans who engage in severe adult-onsent CR[extracted from Michael's post here: http://www.imminst.o...&#entry249450)])

References
1. Nagai M, Takahashi R, Goto S. Dietary restriction initiated late in
life can reduce mitochondrial protein carbonyls in rat livers: western
blot studies. Biogerontology. 2000;1(4):321-8. PMID: 11708213

2. Weindruch R, Walford RL.
Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence.
Science. 1982 Mar 12;215(4538):1415-8.
PMID: 7063854 [PubMed - indexed for MEDLINE]

3. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL.
Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats.
J Gerontol. 1983 Jan;38(1):36-45.
PMID: 6848584

4. Lipman RD, Smith DE, Blumberg JB, Bronson RT.
Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging.
Aging (Milano). 1998 Dec;10(6):463-70.
PMID: 10078316 [PubMed - indexed for MEDLINE]

5. Lipman RD, Smith DE, Bronson RT, Blumberg J.
Is late-life caloric restriction beneficial?
Aging (Milano). 1995 Apr;7(2):136-9.
PMID: 7548264 [PubMed - indexed for MEDLINE]

6. Forster MJ, Morris P, Sohal RS.
Genotype and age influence the effect of caloric intake on mortality in mice.
FASEB J. 2003 Apr;17(6):690-2. Epub 2003 Feb 5.
PMID: 12586746 [PubMed - indexed for MEDLINE]

7. Merry BJ. Food Restriction and the Aging Process. (Photocopy in my posession; damned if I know what book it came from!).

8. Merry BJ. "Dietary Manipulation of Ageing: An Animal Model." In
Bittles AH & KJ Collins, The Biology of Human Ageing, Cambridge
University Press, Cambridge, 1986.

9. Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA.
Abstract
The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.
Free Radic Biol Med. 2004 Apr 15;36(8):1043-57.
PMID: 15059645 [PubMed - indexed for MEDLINE]

10. Pugh TD, Oberley TD, Weindruch R.
Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice.
Cancer Res. 1999 Apr 1;59(7):1642-8.
PMID: 10197641 [PubMed - indexed for MEDLINE]

11. Weindruch R, Gottesman SR, Walford RL.
Modification of age-related immune decline in mice dietarily restricted from or after midadulthood.
Proc Natl Acad Sci U S A. 1982 Feb;79(3):898-902.
PMID: 6977776

12. Spindler SR, Mote PL.
Abstract
Screening candidate longevity therapeutics using gene-expression arrays.
Gerontology. 2007;53(5):306-21. Epub 2007 Jun 15. Review.
PMID: 17570924 [PubMed - indexed for MEDLINE]
[Lifespan curve reproduced (crudely) here, complete with CR data; CR initiated at 14 months -MR]

12: Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR.
Temporal linkage between the phenotypic and genomic responses to caloric restriction.
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5524-9. Epub 2004 Mar 25.
PMID: 15044709 [PubMed - indexed for MEDLINE]

13. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA.
A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
PLoS ONE. 2008 Jun 4;3(6):e2264.
PMID: 18523577 [PubMed - in process]


14. Beauchene RE, Bales CW, Bragg CS, Hawkins ST, Mason RL.
Effect of age of initiation of feed restriction on growth, body
composition, and
longevity of rats.
J Gerontol. 1986 Jan;41(1):13-9.
PMID: 3941250 [PubMed - indexed for MEDLINE]

15. Yu BP, Masoro EJ, McMahan CA.
Nutritional influences on aging of Fischer 344 rats: I. Physical,
metabolic, and longevity characteristics.
J Gerontol. 1985 Nov;40(6):657-70.
PMID: 4056321

16. Ross MH.
Length of life and caloric intake.
Am J Clin Nutr. 1972 Aug;25(8):834-8. No abstract available.
PMID: 5046728 [PubMed - indexed for MEDLINE]

17. Merry BJ.
Molecular mechanisms linking calorie restriction and longevity.
Int J Biochem Cell Biol. 2002 Nov;34(11):1340-54. Review.
PMID: 12200030 [PubMed - indexed for MEDLINE]

18. McCay CM, Crowell MF, Maynard LA.
The effect of retarded growth upon the length of life span and upon the ultimate body size.
J Nutr. 1935 Jul 10;10(1):63-79.

Edited by Brett Black, 11 July 2010 - 05:11 AM.

[Dazed]

I am a little confused to at which point extreme caloric restriction kicks in. I am back on last years diet that often knocks me down to 920 calories for a 5'9" male who has allowed his wieght to blossom to 190 from 165 last year because of a stomache problem. I walk 4 miles a day for exercize and I am 63. I don't feel deprived. An average day for me is:

Breakfast
Oatmeal 1/2 cup
Fiber One 1/2 cup
Ground Flax seed 2 tbs
Dark Cocoa 2 TBS
Banana

Lunch
Boneless skinless chichen breast 5 Oz

Dinner
Romaine Lettuce 2 cups
Raw Spinach 2 cups
Strawberries 8 oz
Blueberries 8 Oz

[benthamite]

Ok, I want to be very clear about this point, because from what I've seen, you are considered a notable figure in online CR circles, and a lot of people seem to pay quite a bit of attention to what you say and believe. So:

You agree, that based on extrapolation from current adult onset caloric restriction studies in rodents, that about a 5% to 10% increase in lifespan is what the average person could expect if they practiced severe caloric restriction? Yes?

It is worth pointing out that Dean Pomerleau, a highly respected figure in the CR community, estimates that his own regime "will probably add at most 8 or 10 years, but it could be half that or a quarter of that." (Though note that Pomerleau started practising CR at the age of 35.)

[Forever21]

re: severest cr will add just 4-8 years to human life

but will i die thin and beautiful?

[Guest]

Personally I do CRON to improve the odds of being able to get any benefit from SENS or similar biomedical research. I decided that for me at least 5 years out of CRON will be sufficient to justify the approach. It is important, that my overall health status will be much better in any case. So to speak, while life span might be not increased by decades, the healthspan is certainly much improved. And possibly I will need this health to get something out of first generation SENS-like therapies.

[niner]

According to my personal preferences, a lifetime filled with enjoyable physical activity and a well-designed and pleasurable diet would trump years of severe caloric restriction, and I think the evidence(of which there is mountains more than CR) is that it may be approximately as beneficial to lifespan and healthspan as CR.

I would have to call this a minority viewpoint. I suppose it might be the case if the CR practitioner was a Cheetos-eating couch potato who just didn't happen to eat very many Cheetos, but in reality people like Michael are engaging in Optimal Nutrition along with CR, thus the moniker CRON. They also address the need for exercise, so their baseline probable lifespan, not accounting for CR, is already above average.

[Logan]

re: severest cr will add just 4-8 years to human life

but will i die thin and beautiful?

More like too thin and unhealthy looking. You're skin will shrivel up more-way too little fat, muscle and overall body mass.

[TheFountain]

I am a little confused to at which point extreme caloric restriction kicks in. I am back on last years diet that often knocks me down to 920 calories for a 5'9" male who has allowed his wieght to blossom to 190 from 165 last year because of a stomache problem. I walk 4 miles a day for exercize and I am 63. I don't feel deprived. An average day for me is:

Breakfast
Oatmeal 1/2 cup
Fiber One 1/2 cup
Ground Flax seed 2 tbs
Dark Cocoa 2 TBS
Banana

Lunch
Boneless skinless chichen breast 5 Oz

Dinner
Romaine Lettuce 2 cups
Raw Spinach 2 cups
Strawberries 8 oz
Blueberries 8 Oz

This seems very nutrient deprived. You need to color up your vegetable intake, add some kale, collard greens, peppers, etc.

[Logan]

I am a little confused to at which point extreme caloric restriction kicks in. I am back on last years diet that often knocks me down to 920 calories for a 5'9" male who has allowed his wieght to blossom to 190 from 165 last year because of a stomache problem. I walk 4 miles a day for exercize and I am 63. I don't feel deprived. An average day for me is:

Breakfast
Oatmeal 1/2 cup
Fiber One 1/2 cup
Ground Flax seed 2 tbs
Dark Cocoa 2 TBS
Banana

Lunch
Boneless skinless chichen breast 5 Oz

Dinner
Romaine Lettuce 2 cups
Raw Spinach 2 cups
Strawberries 8 oz
Blueberries 8 Oz

This seems very nutrient deprived. You need to color up your vegetable intake, add some kale, collard greens, peppers, etc.

Yeah and where are the nuts?

I would eat a little fiber/carbs along with your chicken breast for better protein absorption.

[Forever21]

Here's a good one

Meal 1
Wild Blueberries
Red Raspberries
Black Raspberries
Black Berries
Apple Skin
Walnuts

Meal 2
Big Bowl Salad
-Spinach
-Kale
-Collards
-Broccoli
-Cabbage
-Peppers
-Brussels sprouts
-Celery
-Mushrooms
-Asparagus
-Cucumber
-Tomato paste
-Sweet Potatoes
-Extra Virgin Olive Oil
-Avocado


Meal 3
Tempeh/Salon or Egg salad + veggies
Quinoa + Spinach Salad
Lentil + Spinach soup

Snack
Greek Yogurt
Kefir
Kale Smoothie
Berry Smoothie
Nuts

[JLL]

This thread needs more discussion about the lifespan calculations. Is it really just 4-8 years? Does everyone here on CR really know how little they are gaining?

[Brett Black]

This thread needs more discussion about the lifespan calculations. Is it really just 4-8 years? Does everyone here on CR really know how little they are gaining?

The generalized "calculations"(derived from multiple replicated studies*) are:

1. Rodents subjected to 50% caloric restriction from childhood will experience about a 50% increase in lifespan.

2. Rodents subjected to 50% caloric restriction from adulthood however will only experience about a 15% increase in lifespan.

3. Adult humans(except perhaps for the most morbidly obese) simply cannot tolerate a 50% caloric restriction - it would kill them. Adult humans who start from a healthy weight can only expect to tolerate about a 20% caloric restriction at absolute maximum.

4. Rodent data shows that reducing the level of CR results in a corresponding reduction in lifespan extension. With a 20% caloric restriction(the maximum tolerable level in humans) initiated during adulthood, there is only about a 5% to 10% increase in lifespan in rodents.


Bringing it all together: if rodent data extrapolates reasonably faithfully to humans, the most severe caloric restriction a human adult could tolerate would lead to a 5% to 10% lifespan increase(about 4 to 8 years.) To top it all off, at such a severe level of CR a person would have a BMI of 15 or less and would thus resemble a living skeleton for the entire 50 years of practicing CR that would be necessary for them to gain even this negligible increase in lifespan.


*(Check out the references in my previous posts, particularly the following paper which Michael Rae has describe as "seminal", it is in agreement with these calculations:
"Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence" http://www.ncbi.nlm..../pubmed/7063854)

Edited by Brett Black, 15 July 2010 - 02:25 PM.

[Guest]

I am not an expert on the studies done about CRON, therefore could you elaborate a bit more in detail your reasoning? Some statements appear to be somewhat arbitrary/not in agreement with actual observations in humans.


Why would 20% CR be the "the maximum tolerable" level in humans? And how is the BMI of 15 derived? For example I am a male, 187 cm. I do CRON averaging currently at about 1800 kcal a day (carefully tracking with CRON-O-Meter). I stopped loosing weight at about 61 kg while being moderately active, i.e. cycling to work every day and playing soccer for 2 hours once a week. I have a BMI of about 17,2.

So even if my adlib intake would have been 2200 kcal (actually it was more) I would do a 20% CRON now. Also I am *very* sure that only a hand full of CRONies are in the BMI 15 range, despite a lot of them doing a CR 20% and more (measured against e.g. the governmental set value of 2500 kcal for an average male). I suspect (although not being a in the biological sciences), that the body adjusts to the lower level of calories so that weight-loss approximations for non-chronically CRed people are not fully transferable. Also I do not have a problem with hunger, as I drink a lot and eat filling stuff (usually 2,5 - 3 kg of vegetables, fruits, dairy, oats etc. a day). So I find it hard to agree on the difficulties of doing just even 20% CR in humans.


Also note that there are different motivations for doing CRON. Despite my reasoning above I tend to agree, that a human starting a 30% CR just after maturation will find it hard to get more than 10 years of lifeextension out of it. However, lokking at the available data from primate trials and tests done at CRONies I strongly suspect, that *in addition* their healthspan will be considerably improved, too. Especially for younger CR-folks looking for biomedical progress these 2 effects possibly will make a difference. It is not funny to miss future regenerative therapies because you die a decade too early and are in addition in a not so good overall health state.


For me at least it is the most feasible way to improve my chances to benefit from research such as SENS. 10 years lifespan/15 years healthspan are not the world currently - but they can be, if regenerative medicine keeps progressing at the current speed. Having those additional years can turn out to be decisive. Of course, if you are not part of the lifeextension crowd it doesn't matter for you.

[JLL]

I've brought this up before, but I think CR percentage calculations in humans are meaningless.

What does 10% CR mean for a human? For someone who is used to eat 2,000 kcal per day, it would be 1,800 kcal. For someone who is used to eat 3,000 kcal, it would be 2,700 kcal.

Both are doing 10% CR, by definition, but one is eating 900 kcal more than the other. I seriously doubt that the 2,700 kcal person is getting as many benefits as the 1,800 kcal person.

Maybe we should look at absolute calories instead of percentage reductions? I know the 'setpoint' idea, but I don't find it all that convincing, because it is possible to increase the number of fat cells at any age and thus change the setpoint.

[rwac]

What would 1000-1200 calories count as ?

I went through a stretch of a few months eating very little and sleeping a lot, because I was ill.
I'm ~160 lbs with 18-20% bf and didn't lose any weight.

[Guest]

Maybe - just to make a point - if in addition of being relatively tall I would be an american citizen, my reference kcal-intake would have been likely 3000 kcal/day. From this point of view I am already doing 40% CR. Unlikely, but we see that connecting a 20% CR with an arbitrary BMI of 15 is, well, arbitrary. Also even at a normal/high calorie diet I was far from beeing overweight, although I felt hot all the time.

[Dmitri]

I am not an expert on the studies done about CRON, therefore could you elaborate a bit more in detail your reasoning? Some statements appear to be somewhat arbitrary/not in agreement with actual observations in humans.


Why would 20% CR be the "the maximum tolerable" level in humans? And how is the BMI of 15 derived? For example I am a male, 187 cm. I do CRON averaging currently at about 1800 kcal a day (carefully tracking with CRON-O-Meter). I stopped loosing weight at about 61 kg while being moderately active, i.e. cycling to work every day and playing soccer for 2 hours once a week. I have a BMI of about 17,2.

I agree with you there, BMI of 15 is a bit of stretch, I also did CR a few months ago averaging between 1,500-1,900 calories a day (depending on the day), I also exercised about 45 min-1hour, 3-4 times a week and my BMI never went below 20. In fact my BMI remained steady between 20.4-21 while I was on CR. I suppose in my case it had more to do with being on a high carb diet opposed to the high fat which many member here practice?

[niner]

Brett's argument seems to rest entirely on extrapolation of mouse results to humans. I think that's a dangerous game.

[cojadate]

niner: All the theories about the effect of CR on extending maximum human lifespans are based on extrapolating from animal studies to humans. It'll be a long time before we have anything better.

By the way I find this discussion is extremely interesting. Thanks very much to everyone who has participated so far on, all sides. I'm watching its progress with bated breath.

[Brett Black]

I am not an expert on the studies done about CRON, therefore could you elaborate a bit more in detail your reasoning?

Certainly.

Some statements appear to be somewhat arbitrary/not in agreement with actual observations in humans.

Why would 20% CR be the "the maximum tolerable" level in humans? And how is the BMI of 15 derived?

I based these figures on a number of factors.

First, I assumed that a BMI of 15 was about the minimum BMI that could reasonably expected to be survivable, over the long term, by the average person. I chose this particular BMI based on World Health Orginization BMI classifications, which can be found here:

http://apps.who.int/...ge=intro_3.html (note <16 BMI is "severe thinness" the minimum BMI category listed in the "underweight" section.)

I also based the minimum BMI on several (but admittedly weakly validated) reports of the BMIs of female anorexia sufferers shortly before death(however I think it would be most reasonable to assume that they were probably not trying to achieve "optimum nutrition" at this point.)


For the caloric restriction side of things I used Mifflin-St Jeor equations. These equations have been tested and proven to be about the most accurate metabolic rate calculations currently available, with around 80% of people falling within +/-10% of the calculated figures:

"Validation of several established equations for resting metabolic rate in obese and nonobese people"
http://www.ncbi.nlm....pubmed/12963943

There's a nice online Mifflin-St Jeor calculator specifically developed for CR here:
http://www.scientifi...alth/cron1.html

For the starting weight, against which the level of CR was compared(the so called "set point") I entered a variety of BMIs that are considered within the "Normal Range" by the W.H.O. classifications(18.5 to 24.9.) I did this for both genders, and a variety of ages.

The general results showed that even for people starting at the top of the healthy BMI range, they would drop to around 15 BMI with just a 20% caloric restriction.

For example I am a male, 187 cm. I do CRON averaging currently at about 1800 kcal a day (carefully tracking with CRON-O-Meter). I stopped loosing weight at about 61 kg while being moderately active, i.e. cycling to work every day and playing soccer for 2 hours once a week. I have a BMI of about 17,2.

Being 187cm tall means that you are a bit of an outlier to begin with, and it is known that BMI, which is already a rough tool, becomes even less useful at the extremes. So that probably should be taken into account. What's your age and gender? I can't do the calculations without them.

So even if my adlib intake would have been 2200 kcal (actually it was more) I would do a 20% CRON now. Also I am *very* sure that only a hand full of CRONies are in the BMI 15 range, despite a lot of them doing a CR 20% and more (measured against e.g. the governmental set value of 2500 kcal for an average male).

There's no way I'd use the 2500kcal "average male" calorie intake to compared against, that's far too general of a figure.

I suspect (although not being a in the biological sciences), that the body adjusts to the lower level of calories so that weight-loss approximations for non-chronically CRed people are not fully transferable.

Others have suggested this as a possibility, and they're usually referring to a lowering of basal/resting metabolic rate that might occur after being on CR. I haven't done enough research into this to give a confident answer yet. The short term data I've seen to date only shows a rather small lowering of metabolic rate. I seem to remember that Michael Rae has surveyed the data and come to the conclusion that the evidence doesn't support long-term changes in metabolic rate. Maybe Michael could comment on this.

Here's one of the studies that does at least show short-term decreases in metabolic rate, but only by a measly 6%:
"Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals"
http://www.ncbi.nlm....pubmed/16595757

Also I do not have a problem with hunger, as I drink a lot and eat filling stuff (usually 2,5 - 3 kg of vegetables, fruits, dairy, oats etc. a day). So I find it hard to agree on the difficulties of doing just even 20% CR in humans.

Are you absolutely certain of your caloric intake? What methods do you use to measure it?

Also note that there are different motivations for doing CRON. Despite my reasoning above I tend to agree, that a human starting a 30% CR just after maturation will find it hard to get more than 10 years of lifeextension out of it. However, lokking at the available data from primate trials and tests done at CRONies I strongly suspect, that *in addition* their healthspan will be considerably improved, too. Especially for younger CR-folks looking for biomedical progress these 2 effects possibly will make a difference. It is not funny to miss future regenerative therapies because you die a decade too early and are in addition in a not so good overall health state.


For me at least it is the most feasible way to improve my chances to benefit from research such as SENS. 10 years lifespan/15 years healthspan are not the world currently - but they can be, if regenerative medicine keeps progressing at the current speed. Having those additional years can turn out to be decisive. Of course, if you are not part of the lifeextension crowd it doesn't matter for you.

As I said to Michael, I think putting CR into this type of context makes it a stronger argument.

A few things though. First, it must be understood that caloric restriction is in direct opposition to exercise(ie physical activity that burns calories.) Burning calories by exercising means a person has to eat more calories, and this fundamentally contradicts the basis upon which caloric restriction rests. So exercise should be avoided by those who are seeking to maximise CR. But, obviously, there is mountains of evidence(much more than there is for the positive CR effects of lifespan on humans) that exercise is beneficial to both lifespan and healthspan in humans.

Second, the majority of adults in developed Western countries, upon which average life span is based, are not only lacking in exercise, but they are also overweight and eating diets that often do not follow the recommendations of the major medical and health authorities. Just following conventional mainstream medical and health advice should theoretically extend healthspan noticeably compared to the norm, if not lifespan too(even to within close to the negligible gains projected by the shaky CR evidence, which may not even transfer to humans.)

Third, CR is not proven in humans, or even non-human primates. It is an unknown, a potential risk. If anything, I'd at least be waiting for the results of the first primate studies, which will be available in about a decade, before I considered CR. Assuming a proportional effect of life extension versus time practicing CR, waiting a decade for those results would only decrease the projected total life extension gains by about 6 to 12 months anyway.

I absolutely am interested in life extension personally, which is why I started to look into CR in the first place. I began with a rather excited and enthusiastic mindset, based on the commonly held(but often contradicted or not supported by scientific evidence) beliefs in online CR circles. As I began looking more deeply into the research I was left very disappointed indeed.

There appears to be widespread misconceptions(exaggerations) about the degree of life extension that CR is currently projected to give. I think these misconceptions are being fueled by some intentionally misleading statements within CR circles, as well as by a lot of ignorance within the CR community. My intent is to try to clear up some of these misconceptions.

One example: the front page of the CR Society website currently displays a very prominent graph demonstrating the life extension gains of rodents on CR. What they fail to mention is that the graph only relates to CR started in childhood and that the higher levels of CR shown are not tolerable by humans. When started in adulthood and with a level of CR that is tolerable by humans, the level of life extension is just 1/6 that of the best curve shown in the graph. I find that willfully misleading and completely unacceptable.

Edited by Brett Black, 16 July 2010 - 01:17 AM.

[Guest]

Thanks for your reply. Some comments:

I based these figures on a number of factors.

First, I assumed that a BMI of 15 was about the minimum BMI that could reasonably expected to be survivable, over the long term, by the average person. I chose this particular BMI based on World Health Orginization BMI classifications, which can be found here:

http://apps.who.int/...ge=intro_3.html (note <16 BMI is "severe thinness" the minimum BMI category listed in the "underweight" section.)

I also based the minimum BMI on several (but admittedly weakly validated) reports of the BMIs of female anorexia sufferers shortly before death(however I think it would be most reasonable to assume that they were probably not trying to achieve "optimum nutrition" at this point.)


For the caloric restriction side of things I used Mifflin-St Jeor equations. These equations have been tested and proven to be about the most accurate metabolic rate calculations currently available, with around 80% of people falling within +/-10% of the calculated figures:

"Validation of several established equations for resting metabolic rate in obese and nonobese people"
http://www.ncbi.nlm....pubmed/12963943

There's a nice online Mifflin-St Jeor calculator specifically developed for CR here:
http://www.scientifi...alth/cron1.html

For the starting weight, against which the level of CR was compared(the so called "set point") I entered a variety of BMIs that are considered within the "Normal Range" by the W.H.O. classifications(18.5 to 24.9.) I did this for both genders, and a variety of ages.

The general results showed that even for people starting at the top of the healthy BMI range, they would drop to around 15 BMI with just a 20% caloric restriction.

I see your logic, but as indicated previously there is reason to doubt that those general population approximations are valid for people whose metabolism switched into the CR-state. This is noted at the very website you quoted: http://www.scientifi...alth/cron1.html below the supposed calculator. I do not blame you to use established methods for the general population, especially as I am not aware of a broad literature for CRed people. However, they note, that appearently BMR works differently for CRON people, including providing a couple of studies, than assumed in the calculator they (and you) use. At least I doubt that I and the cases/studies described at the very website you're reffering to are exceptions among the CRON folks. Or maybe I am and I'll be just one of a few chosen that can sustain CRON without being BMI 15.

Being 187cm tall means that you are a bit of an outlier to begin with, and it is known that BMI, which is already a rough tool, becomes even less useful at the extremes. So that probably should be taken into account. What's your age and gender? I can't do the calculations without them.

As I wrote I am a "male", age is mid 20's. Does the BMI depend on ones age? There might be differences in the average BMI of certain age groups, but the formular to calculate it should be the same? You are the expert.

There's no way I'd use the 2500kcal "average male" calorie intake to compared against, that's far too general of a figure.

As if a proposed 20% CR = 15 BMI for everyone wouldn't be less a generalization. However, I agree that we would have to look at individual people. Taller people likely require more kcal a day than smaller people. So where could we start? Do we use a setpoint, e.g. weight under adlib intake? Despite what some CR-calculators might suggest there is not an established method about what constitutes a x% CR in humans (and indeed a number of CRONies refuse to use such measures). In principle we would need a genetical homogenous reference group for each person to observe a supposed setpoint or a kcal-to-sustain-normal-weight value. Also people react differently to kcal intake, as e.g. recent studies showed (I can look them up) that humans to different degrees burn unused kcal into heat than storing them in fat cells.

Others have suggested this as a possibility, and they're usually referring to a lowering of basal/resting metabolic rate that might occur after being on CR. I haven't done enough research into this to give a confident answer yet. The short term data I've seen to date only shows a rather small lowering of metabolic rate. I seem to remember that Michael Rae has surveyed the data and come to the conclusion that the evidence doesn't support long-term changes in metabolic rate. Maybe Michael could comment on this.

Here's one of the studies that does at least show short-term decreases in metabolic rate, but only by a measly 6%:
"Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals"
http://www.ncbi.nlm....pubmed/16595757

I've got another study that shows a long term decrease: "Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight"; note especially the long run 30% reduction in non-resting energy expenditure, which might give another strong bias into the "activity" parameters used by the CRON-calculator.
http://www.ajcn.org/...t/full/88/4/906

Also even 6% is 150 kcal less required every day if we talk about a hypothetical 2500 adlib kcal person. It would allow me to eat 1800 kcal at BMI 17,4 instead of 1950 kcal. Also we have to distinguish reduced energy expenditure due to reduced body mass and due to reduced metabolic rate. Both contributes. However, there is indeed not much research available about this. Maybe we could collect BMI and corresponding non-cheating-kcal-intake data from CRON people to bring some light into the topic.

Are you absolutely certain of your caloric intake? What methods do you use to measure it?

As I wrote I am using CRON-O-Meter, meaning I put my daily meal plan into it to track kcal and nutritions. I measure the portions of food and use the labels at the package, respectively. I usually do not cheat.

A few things though. First, it must be understood that caloric restriction is in direct opposition to exercise(ie physical activity that burns calories.) Burning calories by exercising means a person has to eat more calories, and this fundamentally contradicts the basis upon which caloric restriction rests. So exercise should be avoided by those who are seeking to maximise CR. But, obviously, there is mountains of evidence(much more than there is for the positive CR effects of lifespan on humans) that exercise is beneficial to both lifespan and healthspan in humans.

In principle I tend to agree. CR-people can not be professional sportsmen without leaving CR. Also the benefits of CR and exercise are not synergistic. However, as of my experience one can do 20-30 running a day even at CR. It probably reduces your BMI if you do not compensate with more kcal. Also I see CR as a kind of a bet: I bet, that animal data is to some degree transferable to humans. The monkey studies suggest that the CR-effect exists in primates and that I am likely not worse of than adlib people. Final data from the trials won't be available for another 10 or 15 years, so waiting is not an option for me. Indeed the rhesus monkey trial is in principle very positiv if you look at the onset of aging related diseases and death. But as there are quite a number of dead subjects due to accidents and husbandry misconduct the overall mortality picture is less impressive, though still in favour of CRON. I am not sure what to think about the latter point.

But I am sure, that 100% immunity to diabeties can't be reached by any amount of exercise. Also CRON-people monitored at the UoW have better blood work and cardiovscular functioning than model-athlets. Though it still will take years untill we know how the final story turns out.

Second, the majority of adults in developed Western countries, upon which average life span is based, are not only lacking in exercise, but they are also overweight and eating diets that often do not follow the recommendations of the major medical and health authorities. Just following conventional mainstream medical and health advice should theoretically extend healthspan noticeably compared to the norm, if not lifespan too(even to within close to the negligible gains projected by the shaky CR evidence, which may not even transfer to humans.)

Yes, its still a bet, that the favourable development at the non-human primates front are transferable to humans. But as I understand it, CR-gains are meant to be in relation to non-obese/overweight reference people. As I already follow the common sensical advices (not smoking, lots of vegetables/fruits/fish/nuts/oats, some essential supplements, some exercise) the only way to improve lifespan/healthspan is IMO CRON. And the evidence currently is more in favour that it will work than against it. If they publish convincing evidence that it'll not extend health/life compared to my imaginary non-CRed identical twin, or by less than 5/10 years life/healthspan, I am going to give a Pizza-party for my friends. But this is not (yet) the case.

Third, CR is not proven in humans, or even non-human primates. It is an unknown, a potential risk. If anything, I'd at least be waiting for the results of the first primate studies, which will be available in about a decade, before I considered CR. Assuming a proportional effect of life extension versus time practicing CR, waiting a decade for those results would only decrease the projected total life extension gains by about 6 to 12 months anyway.

I absolutely am interested in life extension personally, which is why I started to look into CR in the first place. I began with a rather excited and enthusiastic mindset, based on the commonly held(but often contradicted or not supported by scientific evidence) beliefs in online CR circles. As I began looking more deeply into the research I was left very disappointed indeed.

How old are you? If you are still young you probably can wait. Otherwise, and if you are concerned about life extension, you should weight the evidence against the losses (monitoring food, eating less, being extra lean, reduced innate immune response etc. - although the latter can be argued about). We don't know the life extension/ healthspan gains, although I tend to agree that they will be moderate, even more if you start late and doing something as 5% CR (whatever this means in humans).

There appears to be widespread misconceptions(exaggerations) about the degree of life extension that CR is currently projected to give. I think these misconceptions are being fueled by some intentionally misleading statements within CR circles, as well as by a lot of ignorance within the CR community. My intent is to try to clear up some of these misconceptions.

One example: the front page of the CR Society website currently displays a very prominent graph demonstrating the life extension gains of rodents on CR. What they fail to mention is that the graph only relates to CR started in childhood and that the higher levels of CR shown are not tolerable by humans. When started in adulthood and with a level of CR that is tolerable by humans, the level of life extension is just 1/6 that of the best curve shown in the graph. I find that willfully misleading and completely unacceptable.

Again we have to argue about what level of CRON is tolerable by humans, also I am not member of the CR-Society. Anyway, I agree that a lot of life extension CRONies appear to be overoptimistic - sometimes I even have the feeling, that their simplistic expectation of living to 120+ due to their late-life adult onset CR prevents them from actively supporting actual life extension research such as SENS. Possible reasoning: "I am 50 and just started CR, I will live to 120, so I have 70 years left. Great. Just lay back and wait untill biomedical anti-aging is served free house."

However, just to repeat, my motivation: regenerative medicine indeed is progressing rapidly in recent years. I am not entirely sure about when they will be able to to do comprehensive revajunation (Aubreys timeframe is IMO overoptimistic), but I am certain that it will happen sooner or later. Just a number of years in health/lifespan can mean the difference between ending in a CRYO-tube or as a biological young supercentenarian.

[Brett Black]

According to my personal preferences, a lifetime filled with enjoyable physical activity and a well-designed and pleasurable diet would trump years of severe caloric restriction, and I think the evidence(of which there is mountains more than CR) is that it may be approximately as beneficial to lifespan and healthspan as CR.

I would have to call this a minority viewpoint. I suppose it might be the case if the CR practitioner was a Cheetos-eating couch potato who just didn't happen to eat very many Cheetos, but in reality people like Michael are engaging in Optimal Nutrition along with CR, thus the moniker CRON. They also address the need for exercise, so their baseline probable lifespan, not accounting for CR, is already above average.

Caloric restriction in humans presents many unknowns and potential risks. Along with the fact that it has yet to be proven to have any lifespan or healthspan extending effects in humans or other primates, there is the possibility that it carries with it unknown risks which could actually degrade lifespan and healthspan. Even if we are happy to directly extrapolate CR results from rodents to humans it seems the benefits will likely not be all that significant.

On the other hand, mainstream conventional health and dietary recommendations are much better proven in humans, have far more evidence behind them, and thus present a far surer gamble. They should deliver something close to the negligible projected benefits of CR without the risks and trouble of CR.

I question the ability of CR practitioners to engage in exercise in any great way, since exercise leads directly to a higher calorie intake which is diametrically opposed to the basic principle of CR. We know that exercise is beneficial for health and lifespan, and avoiding it for the cause of CR might cancel out these benefits.

I wouldn't call any of these points part of a "minority viewpoint."

[Brett Black]

I've brought this up before, but I think CR percentage calculations in humans are meaningless.

What does 10% CR mean for a human? For someone who is used to eat 2,000 kcal per day, it would be 1,800 kcal. For someone who is used to eat 3,000 kcal, it would be 2,700 kcal.

Both are doing 10% CR, by definition, but one is eating 900 kcal more than the other. I seriously doubt that the 2,700 kcal person is getting as many benefits as the 1,800 kcal person.

Yes it's all very problematic.

Here's a wild theory: what if humans are already genetically wired, as well as socially conditioned, to practice caloric restriction? What if we already are living longer lives compared to many species because we are naturally in a constant state of caloric restriction compared to them?

This might help to explain the seemingly narrow range of "normal" caloric intake that most humans may have compared to rodents, and also why we cannot survive such severe reductions to our normal "ad lib" intake compared to rodents.

With our big brains we can plan much better for the future and have been doing so for hundreds of thousands of years. The result may be that humans have been intentionally restricting their food intake for countless millenia because we were aware that storing food for leaner future times makes a lot of sense.

Couple this with the fact that we are very social creatures who share food and we could easily imagine very serious consequences("executions" leading to reduced reproduction rates) for those individuals who were perceived to be eating too much of the tribe's food. The evolutionary consequences of these forces would then select for CR'ed humans.

Maybe we should look at absolute calories instead of percentage reductions? I know the 'setpoint' idea, but I don't find it all that convincing, because it is possible to increase the number of fat cells at any age and thus change the setpoint.

How about this: we make a new "set point", and we place it at the point at which caloric intake is so low that 50% of individuals will die when subjected to it.

Sort of like the LD50, call it the CR50 perhaps. This seems like a less subjective yardstick that we can use, and which we already have decent data on in rodents, and maybe a better chance of calculating it in humans too than a nebulous "ad lib" set point.

Then all caloric restriction figures are based on the percent of calories a person is ingesting above the level that is simply necessary to keep them alive.

Edited by Brett Black, 16 July 2010 - 08:52 AM.

[capsun]

Any increase over maximal lifespan is quite significant since most humans don't ever reach close to their maximal lifespan.