25 replies to this topic

[zoolander]

Calorie restriction, for those who have been on mars for the last decade, aims to improve one's health an slow the rate aging. There are many suggested ways that this is thought to happen. The following are thought to be mechanisms by which CR acts to improve health and slow the rate of aging:

• hormesis
• reduction in free radicals/glycation
• insulin signalling
• Activation of SIRT1
• and so on...

What about calorie restriction, by increasing energy expenditure as opposed to calorie restriction by diet. This seems like the better option to me. Restricting the calories in the diet essentially decreases opportunities to get essential nutrients. For example, if my daily calorie requirements were 2500kCal and I reduced this by 20% then that means I need to fit all my essential nutrients into 2000kCal instead of 2500kCal. Now I know that most people on CR have very structured diets that are nutrient dense but doesn't it seem like an easier option to open up (increase) more opportunities by increasing energy expenditure through exercise whilst not increasing calorie intake. For example, as above my requirements are 2500kCal and instead of restricting the diet by 20% (i.e 500kCal) I simply exercise and expend 600kCal in the day whilst maintaining my normal intake. That's still a negative energy balance of 20% however I now have a larger place to fit my needed nutrients.

So let's say we call this CE or Calorie Expenditure. Exercise in moderation, by the way, has also been shown to improve one's health and to slow the aging process. Some of the suggested mechanism are as follows:

• hormesis (1)
• combats free radical (2)
• insulin signalling (3)
• Activation of SIRT1 (4)
• and so on...
  
  Looks a lot like the list provided for CR.

You could also restrict calories by combining the two. One of the above appears to be all about decreasing your options whilst the other appears to be about increasing your options. Exercise, most of the time, is fun and it's benefit go well beyond the physical. Exercise, especially for the elderly, is a great interactive social environment that keeps your mind working. I can't really see calorie restricting by diet being much fun at all. Continually calculating and weighing to make sure you're on top of things. It doesn't sound very social either. It's hard enough being a vegetarian at a social gathering let alone being on a calorie restricted nutrient dense diet. "Waiter, I ordered the CR option instead of the 50/50 beef/chicken split"

Anyhow, perhaps this has been discussed at length in another thread. I just thought that this would be a great discussion. I think I've been calorie restricting/expending for the last 10 years of my life without knowing because I'm very active and have a very clean diet. I've got some of the signs of what's been seen with calorie restriction in primates. I look younger than I really am and I'm a lot more energetic than my fellow monkeys....I mean 36 year olds.

Thoughts?

Edited by zoolander, 10 June 2008 - 10:54 AM.

[Ben]

I've pondered this myself but then I thought: Doesn't calorie restriction work because of something in food that people who are calorie restricted are getting less of?

This however doesn't affect my view towards calorie restriction (against), the huge negatives that come with it (mood, physical appearance) do that. Even if exercise is inferior to it, in terms of life extension (who really knows?), it's still a much more enjoyable way to extend one's life and enhance one's enjoyment of it.

I can't see the logic behind calorie restriction.

Edit: Forgive my ignorance. As you can probably tell I know little of CR's mechanism.

Edited by Ben - Aus, 10 June 2008 - 11:30 AM.

[zoolander]

They're valid points Ben

[FunkOdyssey]

I've pondered this myself but then I thought: Doesn't calorie restriction work because of something in food that people who are calorie restricted are getting less of?

Methionine restriction produces similar effects to CR, maybe that is what you were thinking of?

[Ben]

I've pondered this myself but then I thought: Doesn't calorie restriction work because of something in food that people who are calorie restricted are getting less of?

Methionine restriction produces similar effects to CR, maybe that is what you were thinking of?

I was thinking that the more you eat the more likely you are to consume more AGEs.

e, this methionine restriction is interesting though.

Edited by Ben - Aus, 10 June 2008 - 01:12 PM.

[Athanasios]

I found the info in this video very enlightening on the CR vs. Exercise topic and in fact has influenced my diet and supplement regimen greatly:

Is Caloric Restriction the Key to a Longer and Healthier Life? (Luigi Fontana)...(about 30 mins)
http://www.edmontona...igi_Fontana.wmv

and I thought this one was worth the watch as well and is one of the reasons I plan to switch to calorie restriction when I am in late my 50s or early-mid 60s:

Mechanisms by which Caloric Restriction Better Preserves Skeletal Muscle Mass & Function with Aging
http://www.edmontona...Russ_Hepple.wmv

[Athanasios]

To follow up and summarize, CR has improvements in a few areas over exercise alone such as:

• better fasting glucose
• better blood pressure as age increases
• better preservation and function of muscle at advanced ages
• much lower inflamation: C-reactive Protein, IL-6, TNF-alpha, etc
• and due to low inflamation: smaller values for common carotid artery intima thickness and greater heart elasticity

When it comes to CR via increased calorie expenditure these are the most relevant studies I know of:
First study: http://jap.physiolog...stract/59/3/826 and the follow-ups:

http://jap.physiolog...tract/70/4/1529

Interaction between exercise and food restriction: effects on longevity of male rats
J. O. Holloszy and K. B. Schechtman
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

Male rats that exercise in running wheels have a longer average survival than freely eating sedentary controls but, in contrast to food-restricted sedentary controls of the same weight, show no extension of maximal life span (J. Appl. Physiol. 59: 826-831, 1985). To test the possibility that exercise may counteract a life-extending effect of decreased availability of energy for certain biological processes such as cell proliferation, we examined the combined effects of exercise and food restriction on longevity of male rats. As before, wheel running improved average length of life, 978 +/- 172 vs. 875 +/- 175 (SD) days, for the sedentary controls (P less than 0.01) without increasing maximal life span. Paired-weight controls, food restricted (approximately 30% below ad libitum) to weight the same as the runners, showed increases in both average (1,056 +/- 144 days) and maximal life span. Food-restricted runners, with intake restricted to the same extent (approximately 30%), had an increased mortality rate over the first approximately 50% of their survival curve up to approximately 900 days of age; their average life span (995 +/- 226) was similar to that of the control group of runners and shorter than that of their paired-weight food-restricted sedentary controls (1,088 +/- 159 days, P less than 0.05). However, after approximately 900 days of age the food-restricted runners' survival became similar to that of the food-restricted sedentary groups, with a comparable increase in maximal life span. Thus the exercise did not counteract the increase in maximal life span induced by food restriction.

http://jap.physiolog...stract/82/2/399

Mortality rate and longevity of food-restricted exercising male rats: a reevaluation
John O. Holloszy

Mortality rate and longevity of food-restricted exercising male rats: a reevaluation. J. Appl. Physiol. 82(2): 399-403, 1997.---

Food restriction increases the maximal longevity of rats. Male rats do not increase their food intake to compensate for the increase in energy expenditure in response to exercise. However, a decrease in the availability of energy for growth and cell proliferation that induces an increase in maximal longevity in sedentary rats only results in an improvement in average survival, with no extension of maximal life span, when caused by exercise . In a previous study (J. O. Holloszy and K. B. Schechtman. J. Appl. Physiol. 70: 1529-1535, 1991), to test the possibility that exercise prevents the extension of life span by food restriction, wheel running and food restriction were combined. The food-restricted runners showed the same increase in maximal life span as food-restricted sedentary rats but had an increased mortality rate during the first one-half of their mortality curve. The purpose of the present study was to determine the pathological cause of this increased early mortality. However, in contrast to our previous results, the food-restricted wheel-running rats in this study showed no increase in early mortality, and their survival curves were virtually identical to those of sedentary animals that were food restricted so as to keep their body weights the same as those of the runners. Thus it is possible that the rats in the previous study had a health problem that had no effect on longevity except when both food restriction and exercise were superimposed on it. Possibly of interest in this regard, the rats in this study did considerably more voluntary running than those in the previous study. It is concluded that 1) moderate caloric restriction combined with exercise does not normally increase the early mortality rate in male rats, 2) exercise does not interfere with the extension of maximal life span by food restriction, and 3) the beneficial effects of food restriction and exercise on survival are not additive or synergistic.

Edited by cnorwood, 10 June 2008 - 08:17 PM.

[Mind]

I would say from the perspective of the very basic mechanism of damage accumulation within and between cells, CR would be superior to exercise. More calories and higher metabolism means more damage. I suppose some of the benefits of exercise have a beneficial holistic-type effect on the mind and body and counteract to some degree the extra damage that accumulates.

I do agree with your premise that eating a little more and having more energy for fun energetic activities is more appealing than CR. In my view, CR is basically putting your body in a state as close to hibernation/stasis as possible. If your body isn't doing anything, then it won't wear out very fast. I know, it is a very simplistic view (positive protective processes come into play as well), but that is how I see it from a overall general perspective.

[edward]

There is a video posted on here somewhere, wherein a CR researcher shows the results of a CR study where the rats were divided into 4 groups, CR, CR + Exercise, Exercise alone and Adlib sedentary. It showed of course that CR signifigantly extended lifespan, CR + Exercise did a little bit better (but not much), Exercise alone beat the controls signifigantly but didn't come close to CR or CR+Exercise.

Obviously exercise will help, I think exercise plus some IF and good supplementation, is a pretty good plan, especially if some of the exercise is done during the fasting phase (may help activate those survival genes) but exercise alone I don't think will do it.

[edward]

Now I do see the point of setting your calories constant, then adding exercise which will increase your carloric needs, burn up extra calories and put you in an "artificially created" CR state as in now since you need more you are calorie restricted but you still have the extra calories to get in the nutrients you need. The rub is that the exercise will increase your nutrient needs so now you need more nutrients. You will also be a lot hungrier.

[Athanasios]

There is a video posted on here somewhere, wherein a CR researcher shows the results of a CR study where the rats were divided into 4 groups, CR, CR + Exercise, Exercise alone and Adlib sedentary.

Yep, the graph was in the "Is Caloric Restriction the Key to a Longer and Healthier Life?" video I posted and was based on the studies I posted.

[Athanasios]

Now I do see the point of setting your calories constant, then adding exercise which will increase your carloric needs, burn up extra calories and put you in an "artificially created" CR state as in now since you need more you are calorie restricted but you still have the extra calories to get in the nutrients you need. The rub is that the exercise will increase your nutrient needs so now you need more nutrients. You will also be a lot hungrier.

The biggest rub is no maximal lifespan increase via that route.

[edward]

I'd have to look back at the study but I think the exercise group was fed ad lib so with increased activity (and repair from activity) their energy requirements would increase and their food consumption would increase.

But if the same group of rats, humans whatever kept the calorie content of their diet set at x = caloric intake of ad lib sedentary. Then they exercised (keeping the caloric intake the same = x) they would be forcing themselves into CR because they now require more calories which they arent getting. Its a subtle difference but say a human with caloric needs of 2500 calories burned 400 calories a day exercising, another 200 extra in metabolism boost and repair of tissues, well that would be the equivalent of a sedentary human of the same height and weight eating 1900 calories.

Its sort of a trick your way into doing CR while eating more calories because your needs have changed but your calories haven't. Still the same principles apply, you would have to meticulously count calories, not only that but factor in expenditure, all you are really gaining is more calories to work with.

Edited by edward, 10 June 2008 - 10:21 PM.

[Athanasios]

I'd have to look back at the study but I think the exercise group was fed ad lib so with increased activity (and repair from activity) their energy requirements would increase and their food consumption would increase.

From the abstract:
http://jap.physiolog...stract/82/2/399
Male rats do not increase their food intake to compensate for the increase in energy expenditure in response to exercise.

[edward]

gotcha
also the next sentence:

"However, a decrease in the availability of energy for growth and cell proliferation that induces an increase in maximal longevity in sedentary rats only results in an improvement in average survival, with no extension of maximal life span, when caused by exercise."

[edward]

the graph, I was mistaken, the oldest food restricted runner died earlier than the oldest food restricted CR animal


triangle: ad lib
circle: exercise only
diamond: food restricted runners
square: food restricted sedentary

Edited by edward, 10 June 2008 - 11:54 PM.

[niner]

In terms of mechanisms, no one mentioned autophagy. It is upregulated in CR. Any effect from exercise? (My guess would be no.)

[Shepard]

In terms of mechanisms, no one mentioned autophagy. It is upregulated in CR. Any effect from exercise? (My guess would be no.)

Perhaps.

Biochem Soc Trans. 2007 Nov;35(Pt 5):1314-6.
mVps34 is activated by an acute bout of resistance exercise.
Mackenzie MG, Hamilton DL, Murray JT, Baar K.

James Black Centre, University of Dundee, 28 Dow Street, Dundee DD15EH, U.K. m.g.mackenzie@dundee.ac.uk

Resistance-exercise training results in a progressive increase in muscle mass and force production. Following an acute bout of resistance exercise, the rate of protein synthesis increases proportionally with the increase in protein degradation, correlating at 3 h in the starved state. Amino acids taken immediately before or immediately after exercise increase the post-exercise rate of protein synthesis. Therefore a protein that controls protein degradation and amino acid-sensitivity would be a potential candidate for controlling the activation of protein synthesis following resistance exercise. One such candidate is the class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting mutant 34). Vps34 controls both autophagy and amino acid signalling to mTOR (mammalian target of rapamycin) and its downstream target p70 S6K1 (S6 kinase 1). We have identified a significant increase in mVps34 (mammalian Vps34) activity 3 h after resistance exercise, continuing for at least 6 h, and propose a mechanism whereby mVps34 could act as an internal amino acid sensor to mTOR after resistance exercise.

PMID: 17956340 [PubMed - indexed for MEDLINE]

And, you've got some autophagic regulation by AMPK. Resistance exercise and AMPK.

Edited by shepard, 11 June 2008 - 04:14 AM.

[edward]

In terms of mechanisms, no one mentioned autophagy. It is upregulated in CR. Any effect from exercise? (My guess would be no.)

That is a good point. See this study Autophagy as a mechanism for CR life extension

Attached Files

•  autophagy_cr.pdf   470.25KB   66 downloads

Edited by edward, 11 June 2008 - 07:45 PM.

[Athanasios]

If the problem was difference in autophagy, instead of T3 or something else, I would think the increase in calories via postprandial glucose surge or amino acids would affect it more than the exercise. Autophagy has been shown to be required for extended lifespan in CR wormies, so it is definitely possible, but it could be some other factor as well.

FWIW, right now, my response to the CR data and resveratrol data has been to intermittent fast and take resveratrol while minimizing glucose surges and other postprandial responses on eat days.

Edited by cnorwood, 11 June 2008 - 10:07 PM.

[Alpha-Frequency]

How do you Restrict Methionone???

[zoolander]

I'm a bit behind the times here. perhaps someone can refer me to a good reference book for calorie restriction or a good reference review paper.

What is (with humans) the cut off point for calories. 10% restricted...15%, 20%?

[Karomesis]

No offense ZOO, but I think most of the intelligent members here are wise enough to know that CR anything won't result in significant LE.

I've drawn this analogy before, but it's similar to investing; higher risks produce greater returns. You think venture capitalist are happy with anything less that an 80-90% internal rate of return? NO. and as RADICAL life extensionists we should be aiming for the same kinds of returns. not 7% mutual fund bullshit.

calorie restriction is a horse that has not only been beaten to death....it has been ground into a fine powder for use in cosmetics at this point. I'd place my money on CR or especially IF being similar to the way we're SUPPOSED to be eating and living. There will only be very slight improvements on LS with this lifestyle. we need to take very seriously new stem cell developments like this http://www.cytoritx.com/us/index.html and gene therapies like this http://www.scienceda...80520090529.htm if we are to have any significant impact on maximum LS.

[Athanasios]

I'm a bit behind the times here. perhaps someone can refer me to a good reference book for calorie restriction or a good reference review paper.

What is (with humans) the cut off point for calories. 10% restricted...15%, 20%?

This is a good review:
http://jama.ama-assn.../full/297/9/986
In it they cite a study that shows 45% as too much but the CR society at ~30% as beneficial.

All of Pubmed's Fontana's Studies

About time to move the thread to CR Forum?

Edited by cnorwood, 12 June 2008 - 01:56 AM.

[edward]

No offense ZOO, but I think most of the intelligent members here are wise enough to know that CR anything won't result in significant LE.

I so disagree with this, CR is the only thing we have right now that has been proven in repeated trials to extend mean and maximal lifespan signifigantly end of story. Other hopeful things, deprenyl, resveratrol etc. are very promising only with both of these compounds dose is critical Deprenyl with its very narrow dose window of effects and Resveratrol with extremely high doses being the most likely to have positive effects but we really don't know.

I've drawn this analogy before, but it's similar to investing; higher risks produce greater returns. You think venture capitalist are happy with anything less that an 80-90% internal rate of return? NO. and as RADICAL life extensionists we should be aiming for the same kinds of returns. not 7% mutual fund bullshit.
calorie restriction is a horse that has not only been beaten to death....it has been ground into a fine powder for use in cosmetics at this point. I'd place my money on CR or especially IF being similar to the way we're SUPPOSED to be eating and living. There will only be very slight improvements on LS with this lifestyle. we need to take very seriously new stem cell developments like this http://www.cytoritx.com/us/index.html and gene therapies like this http://www.scienceda...80520090529.htm if we are to have any significant impact on maximum LS.

We are talking much greater than 7%, and until technology offers us better options CR looks pretty good. Edit: It will also best allow us to be alive when technology comes through, furthermore alive with less damage to clean up and thus able to benefit from the technology.

Personally for many reasons I have mentioned I am not doing CR, but I am trying to incorporate IF into my diet based on its favorable comparison to CR and similar mechanisms. Also taking Resveratrol and everthing else under the sun

Edited by edward, 12 June 2008 - 02:55 AM.

[TianZi]

As has already been mentioned in one or more posts above, there have been a few studies showing better life extending results when CR is combined with exercise, versus CR alone, so it isn't an "either / or" kind of thing. However, to date there is no firm evidence that exercise by itself can increase maximal lifespan (the evidence tends to show that it doesn't), although it definitely can increase average lifespan. It's worth noting in passing that the recent UK identical twin study did show that exercise can slow the biological rate of aging (at least judging from telomere length in immune cells).

If (I'd say "when") we discover a true CR mimetic in the future (resveratrol at an optimal dose and optimal formulation seems the best current candidate), it will be interesting to see how a vigorous life-long exercise regimen impacts life expectancy for those taking the mimetic, since a strict CR diet makes vigorous exercise difficult and limits its potential benefits.

Edited by TianZi, 24 June 2008 - 06:45 AM.