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CR Effects Not Due to Fewer Calories....


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#31 kismet

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Posted 20 July 2008 - 11:24 PM

What are the problems of taking care of lab. mice so that they can achieve mean and max. life spans comparable to historical controls anyway?
Thinking in layman's terms, it can't be that difficult. Why don't researchers put more effort into it, if it is a recognised problem?
Is there any chance that all those animals observed in such a study have a shorter life span due to chance or a genetic mutation and not bad husbandry? I guess that is very unlikely..

AGEs may contribute more to aging than we thought, but are they the sole cause or only mechanism of action by which CR works, still I don't think so.

#32 niner

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Posted 21 July 2008 - 05:24 AM

This question of poor animal husbandry has come up multiple times in the past. An intervention is reported to lengthen lifespan relative to controls, but then it's pointed out that the controls are not living as long as the optimally husbanded animals. The hole in the logic here is that most of us are not optimally husbanded... I live in a stressful world with a sub-optimal diet and genetics. If an intervention is compensating for these sub-optimalities in some way, then it would be valuable to me and others like me. It would be interesting to know the secrets of the expert rodent caretakers. Maybe we could learn something useful from them. Are they secretly converting their rats to Seventh Day Adventists?

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#33 TianZi

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Posted 21 July 2008 - 06:46 AM

Raw, steamed and boiled foods. Ugh. I can eat sushi, steam dumplings (dim sum), and soup from time to time, but prefer grilled and fried foods. Although I was aware that fried foods should generally be avoided, I was unaware that grilled food was not a healthy choice.

#34 TianZi

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Posted 21 July 2008 - 06:49 AM

Tuesday, July 15, 2008
Eating Less May Slow Aging Process
Cutting just 300 calories a day slows metabolism, tissue failure, study says

(HealthDay News) -- Cutting just 300 to 500 calories a day from your diet could be the key to slowing the signs of aging and living longer, according to a new study.

Studies have long shown that reducing calorie intake slows the aging process in rats and mice. A popular theory is that fewer daily calories decreases production of the thyroid hormone triiodothyronine (T3), which then slows metabolism and tissue aging.

A new study, by Saint Louis University researchers, found this hormone decrease occurs when humans regularly skip rich desserts or substitute a turkey sandwich for a Big Mac and fries every day.

"Our research provides evidence that calorie restriction does work in humans like it has been shown to work in animals," study lead author Edward Weiss, associate professor of nutrition and dietetics at Saint Louis University's Doisy College of Health Sciences, said in a prepared statement. "The next step is to determine if this in fact slows age-related tissue deterioration. The only way to be certain, though, is to do a long-term study."

The findings, published in the June 2008 issue of Rejuvenation Research, are based on a study of healthy but sedentary, non-smoking, 50- to 60-year-old men and post-menopausal women. For a year, the volunteers participated in either: a calorie-restriction group that cut their daily calorie intake by 300 to 500 calories per day; a group that stayed on their regular diet and exercised regularly; or a group that maintained its normal routine.

While those in the calorie-restriction and exercise groups both lost body fat mass, only those in the calorie restriction group also had lower levels of the thyroid hormone.

Although a long-term study is still needed to determine if reducing T3 levels through calorie restriction does indeed slow the aging process, Weiss said cutting back on calories is a good idea.

"There is plenty of evidence the calorie restriction can reduce your risks for many common diseases including cancer, diabetes and heart disease," Weiss said. "And you may live to be substantially older."

Weiss warned that while cutting calories, people need to maintain a healthy diet by eating nutrient-rich foods. He noted that long-term slowing of the metabolism could also make people more prone to weight gain over time.

The key to maintaining a healthy weight, Weiss said, is keeping a consistent diet and exercising regularly.


So What about the slowing of aging, by decreased metabolic rate and decreasing the consumption of a finite amount of battery, so to speak?


The idea that CR extends lifespan primarily through slowing the metabolic rate has been thoroughly discredited, to my knowledge.In studies comparing rats on CR alone vs. rats with a combined exercise / CR regimen, the rats on the combined regimen lived a bit longer on average, and had a higher metabolic rate.

Edited by TianZi, 21 July 2008 - 06:51 AM.


#35 luminous

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Posted 22 July 2008 - 01:38 AM

I've embarked on a new way of eating. I tried in vain to do the low carb thing but found that I simply just don't like meat or eggs that much. Cheese is okay, but it gets old (no pun intended). I just finished a book called "Eat to Live" and nearly every single claim in it is well-sourced and backed up by studies. The book says to look for foods with a high nutrient-to-calorie ratio. When you do that, raw green leafy vegetables come out the winner--by a wide margin--over animal foods. Fruits and cooked vegetables are a close second. If 90% of your daily diet consists of these high-nutrition foods, you end up eating a large volume of food. Daily calories plummet to CR or near-CR levels. The author makes a very good case for adopting this way of eating. I think the high volume of food gives this eating plan a fighting chance for becoming a sustainable form of CR while providing a high level of nutrients. If indeed it's high nutrients rather than calorie restriction itself that contributes to longevity, then I think I've stumbled onto something great. (just my opinion)

#36 kenj

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Posted 22 July 2008 - 11:47 AM

>>> I've embarked on a new way of eating.................. <<<

Vegetables are an absolute winner IMO, - I try to eat as many different colours as possible, raw, steamed and cooked. And, I couldn't restrict my calories long-term without making veggies a huge part of my diet. They fill you up, do not raise blood sugar/insulin much, less IGF-I signaling, making it easy(ier) to function on a low calorie diet, and ultimately slower aging of the body and brain. And, if ya wanna go for a very long life, it makes sense to keep IGF-I low, as it plays a part in growing various cancer forms: Yup, I plan a few years/decades ahead. :-)
Meat, eggs, nuts, are vital additions in smaller portions, but I wouldn't make them the base of my diet. Grain products ands fruits are OK in smaller portions also.

Vegetables are boring stuff to some people, and indeed you don't get the kick that you may get from a juicy steak, - fortunately the body can adapt and change to a diet lower in fats and proteins; we see with long-term CR practioners that they are reaping the Zest of Life from a carefully selected CRON diet, and I've mentioned before the elder Okinawan people thrive on something alike.

>>> foods with a high nutrient-to-calorie ratio <<<

YA know it!

Edited by kenj, 22 July 2008 - 11:48 AM.


#37 maxwatt

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Posted 23 July 2008 - 11:55 AM

CR is still the only intervention that increases maximum life span not AGE inhibitors à la Benfotiamine, right?

Max lifespan was increased by the low-AGE diet, but only compared to the paper's controls. It'd be nice if the study were duplicated by someone who knows how to take care of mice.


I believe some of the variation between different studies in max life span for control groups is due to statistical variation, and does not necessarily indicate poor animal husbandry.

More interesting if a low-age diet and a low-age CR diet resulted in similar lifespans. One would conclude that low-age is responsible for the life-extension effect, not CR. That is a possible implication of the paper I originally posted to start this thread.

#38 sUper GeNius

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Posted 23 July 2008 - 02:52 PM

CR is still the only intervention that increases maximum life span not AGE inhibitors à la Benfotiamine, right?

Max lifespan was increased by the low-AGE diet, but only compared to the paper's controls. It'd be nice if the study were duplicated by someone who knows how to take care of mice.


I believe some of the variation between different studies in max life span for control groups is due to statistical variation, and does not necessarily indicate poor animal husbandry.

More interesting if a low-age diet and a low-age CR diet resulted in similar lifespans. One would conclude that low-age is responsible for the life-extension effect, not CR. That is a possible implication of the paper I originally posted to start this thread.


But what about the eskimos? They don't (didn't?) cook meat or anything. I don't see where ANY AGE-products could have entered their diets. Heart disease was low, but I don't think maximum lifespan was affected.

Edited by FuLL meMbeR, 23 July 2008 - 02:53 PM.


#39 maxwatt

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Posted 23 July 2008 - 05:00 PM

CR is still the only intervention that increases maximum life span not AGE inhibitors à la Benfotiamine, right?

Max lifespan was increased by the low-AGE diet, but only compared to the paper's controls. It'd be nice if the study were duplicated by someone who knows how to take care of mice.


I believe some of the variation between different studies in max life span for control groups is due to statistical variation, and does not necessarily indicate poor animal husbandry.

More interesting if a low-age diet and a low-age CR diet resulted in similar lifespans. One would conclude that low-age is responsible for the life-extension effect, not CR. That is a possible implication of the paper I originally posted to start this thread.


But what about the eskimos? They don't (didn't?) cook meat or anything. I don't see where ANY AGE-products could have entered their diets. Heart disease was low, but I don't think maximum lifespan was affected.


They also don't eat any green vegetables. They don't grow well in snow.

#40 stephen_b

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Posted 23 July 2008 - 07:53 PM

Snow peas maybe?

:~

#41 maxwatt

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Posted 23 July 2008 - 08:25 PM

Snow peas maybe?

:~


They use the peas to catch polar bears.


(Cut a hole in the ice, put the peas round the hole. Hide behind a snow bank. When the polar bear comes to take a pea, jump out and kick him in the ice-hole.)

Seriously: If your only source of vitamin C for 8 months a year is bone marrow, in an environment where daily activities can require you to consume 6000 calories a day mostly staying warm, I think you'd be lucky to make it past 50. Traditionally, when a man was no longer fit enough to hunt, he was left outside to freeze to death at the first shortage of food. A relatively painless death. The women lost their teeth when young from chewing seal hides to make shoes and clothing. The old women fared no better than the men. Modern Inuit people (as they refer to themselves) have welfare payments from the Canadian government and the diet of modern industrial civilization (only an occasional raw seal) with the attendant diseases like diabetes that such a diet causes, not to mention rampant alcoholism. They don't live all that that long either.

#42 mike250

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Posted 24 July 2008 - 02:12 AM

does anybody get stomach issue with raw vegetables. My stomach is not very happy about it.

#43 maxwatt

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Posted 24 July 2008 - 02:40 AM

does anybody get stomach issue with raw vegetables. My stomach is not very happy about it.


Quite common. They are not really all that digestible. The invention of cooking makes up for our inability to digest them properly. Our digestive tract is really quite similar to other primates, from bonobos to green monkeys; we can handle fruit for energy, and leafy greens for protein. Throw in some bugs and an occasional piece of raw meat. Note: there is no guarantee that an ancestral diet will result in maximum lifespan, but it might be easier to digest.

#44 mike250

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Posted 24 July 2008 - 03:42 AM

but would cooking them cause any loss of nutrients or perhaps an increase in AGE- relative to the raw form-

#45 health_nutty

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Posted 24 July 2008 - 03:48 AM

does anybody get stomach issue with raw vegetables. My stomach is not very happy about it.


I hear you. Raw broccoli gives me an amazing amount of gas.

#46 luminous

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Posted 24 July 2008 - 04:04 AM

Are there other supplements (besides carnosine) that can be taked with food to inhibit AGE formation?

http://www.life-enha...ate.asp?ID=1869
Well, this article has some interesting info about supplements and other things that inhibit AGE fomation. First off, I ought to move back to Colorado. Now I know why it's considered the fittest state:

AGE Production May Be Reduced in Food Cooked at High Altitudes

It has been suggested that AGEs are produced at a reduced rate when cooked at high altitudes. Support for that hypothesis is provided by the fact that the boiling point of water is reduced to 90–93ºC (as compared to 100ºC at sea level) at 2–3 kilometers above sea level. Hence, wet cooking for a set period of time would produce only about ½ to ¼ of the AGEs in the food at high altitudes as compared to sea level.

Supplements:

Other Natural Products that Reduce Glycation and AGE Formation

Benfotiamine, a lipid-soluble form of thiamine, vitamin B16
Tomato paste
Resveratrol, inositol, and others
Pyridoxamine, a form of vitamin B6
Carnosine
Curcumin
Rosemary
Alpha-lipoic acid
Flavonoids luteolin, rutin, quercetin, kaempferol, and EGCG

The same article talks about other stuff that inibits AGE formation. I also found several references elsewhere on the internet saying that aspirin inhibits AGE formation as well.

Edited by luminous, 24 July 2008 - 04:08 AM.


#47 krillin

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Posted 24 July 2008 - 04:05 AM

I believe some of the variation between different studies in max life span for control groups is due to statistical variation, and does not necessarily indicate poor animal husbandry.

This case is pretty bad, though. Spindler's controls (max lifespan 1200 days) outlived even the low-AGE group here.

#48 sUper GeNius

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Posted 24 July 2008 - 05:17 AM

I'm going to buy two snakes. Feed one cooked guppies, and the other fresh AGEless live guppies. I'll let you know which lives longer.

#49 fast turtle

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Posted 24 July 2008 - 06:11 PM

The cheapest and easiest to obtain way to reduce AGE formation would be with pyridoxamine -- the stuff is dirt cheap if you order it pure and in bulk from Asian sources.

#50 maxwatt

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Posted 25 July 2008 - 10:49 AM

The cheapest and easiest to obtain way to reduce AGE formation would be with pyridoxamine -- the stuff is dirt cheap if you order it pure and in bulk from Asian sources.


Biostratum applied for investigational drug status, which is why pyridoxamine has not been available in the US, though you can buy it in Canada. Importing it yourself remains a possibility, though the FDA could seize your shipment.

#51 Michael

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Posted 18 September 2008 - 05:42 PM

The cheapest and easiest to obtain way to reduce AGE formation would be with pyridoxamine -- the stuff is dirt cheap if you order it pure and in bulk from Asian sources.

First: the cheapest and easiest (not to mention most effective) way to reduce AGE formation would be by practicing Calorie restriction :) .

Second: this study does not at all prove that "CR Effects Not Due to Fewer Calories": all of the animals were short-lived (see the survival curve of their earlier study, already posted by Krillin):
Posted Image
The very last mouse in that study died at ~140 weeks, which is 980 days; in the current study, whose survival curve I attach to this post, it was even shorter (and CR-high-glycotoxin shorter still). As previously outlined, this is little more than the average LS of a cohort of healthy, well-cared-for, nonobese, genetically clean mice, whose tenth-decile survivorship should certainly exceed 1000 d. Since they don't specify otherwise, I'm assuming that the reason for this was that when they say that the controls were allowed to eat an ad libitum diet, they mean a a literally ad libitum diet -- all the food they can stuff into their furry little faces -- which of course leads to massive obesity and premature death. That's why, as documented in the post op cit, properly-done CR lifespan studies use "AL" controls that are actually 10-20% restricted from literal ad libitum intake, and the CR animals are CRed relative to that: to avoid confounding (and exaggerating) the anti-aging effect of CR per se with mere avoidance of the actively noxious metabolic effects of obesity.

As I reviewed here, Vlassara's group have already shown that people and mice with diabetes suffer exaggerated and very negative effects of dietary glycotoxins; relieving some of this burden from such animals would clearly extend their lives. But that doesn't show that the effects of CR simply reduce to lower glycotoxin intake.

I have little doubt that CR animals fed an exceptionally low-glycotoxin diet would fare even better than CR animals fed an isocaloric high-glycotoxin diet (and I govern myself accordingly), but that's a different thing from showing that mice that are basically being fed normal Calorie levels live longer than animals who are dying early from obesity anyway.

Now, back to that original post for my last point:

The cheapest and easiest to obtain way to reduce AGE formation would be with pyridoxamine -- the stuff is dirt cheap if you order it pure and in bulk from Asian sources.

For reasons given here and in discussion following that post, I would strongly advise against ordering bulk PM from Asia, or anywhere else that you don't have rock-solid information about the source or verifiably independent lab testing using HPLC (not eg. mass spec, as was posted for one company later in that thread), as performed on the raw materials (not just the finished product), and willing to show you both the HPLC curve itself (demonstrating one, clean peak) as well as the overall certificate of analysis results.

Please see, in this connection, my discl0sure -- but A0R has (unfortunately, IMO) stopped offering PM-containing supplements (in part because of the legal threat, but also for other reasons (see below), so that vestige of CoI is largely abrogated.

I hasten to add, moreover, that having recently seen that LEF (who, NB, I have often criticized in the past on various grounds, but of whose supplements' quality I am in general quite confident) is now offering PM, I quite aggressively pursued them for such information -- and while it was a bit of a hassle to get it (they were quite entirely ready and willing to provide a C of A, but were surprised and not initially ready to meet a request as outlined above -- ie, the hassle was absolutely in no way a lack of transparency on their part, but rather attributable to not being familiar with the issue and not having anticipated the request), they did ultimately provide me with such documentation, to my entire satisfaction, and I have accordingly just yesterday ordered their product for my own use.

I am also going to add -- and here there is again an issue of possible vestigal CoI, for which I again urge you to see my discl0sure, tho' I swear up and down that I am saying this in good faith and public interest, not out of any anticipation of personal gain -- that part of the reason for A0R's decision to stop using PM was a recent study (1) showing that, gram for gram, pyridoxal-5-phosphate (P5P/PLP) "was superior to PM in inhibiting accumulation of AGEs, expression of TGF-beta1, type 1 collagen, and fibronectin, and the development of diabetic nephropathy" in "Streptozotocin (STZ)-induced diabetic rats." They are now, accordingly, offering a P5P supplement, which I am also using.

(I know that I have previously ridiculed the use of P5P supplements on the basis that they would be dephosphorylated by phosphatase-mediated hydrolysis in the gut and at the cell membrane before absorption, making them just expensive B6 supplements; well, I was wrong :"-\ . In my defense, I made this statement based on authoritative texts like Modern Nutrition in Health and Disease; it didn't help that companies promoting P5P have often done so quite sloppily or dishonestly, eg by citing studies on intravenous P5P as if they were on oral supplementation, which of course conveniently dodges teh above issue. Despite these generally-reliable sources' statements, however, turns out that, while I have not yet seen a full pharmacokinetic study, there is evidence (eg, (2)) that in addition to this active absorption mechanism, some P5P does survive into the gut intact and is absorbed passively. IAC, whatever the mechanistic explanation, (1) does show that oral P5P does have a quite potent effect on AGE accumulation and AGE-related damage after oral intake, and that's what matters).

This does not mean, however, that I'm simply dropping PM in favor of P5P. (1) does look very promising, but it is only an animal study, and it's the only in vivo study with actual clinical outcomes. PM, by contrast has been taken as far as randomized, double-blind, placebo-controlled, multicenter Phase II human trials, (3) with reasonably good evidence of safety and also of some efficacy, albeit in very unhealthy people and of disappointingly modest magnitude.

Thus, I'm hedging my bets, using a bit of each for the moment, and am very pleased to have a source that I trust for both supplements.

References
1. Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T.
Pyridoxal phosphate prevents progression of diabetic nephropathy.
Nephrol Dial Transplant. 2007 Aug;22(8):2165-74. Epub 2007 Apr 20.
PMID: 17449494 [PubMed - indexed for MEDLINE]

2. Mehansho H, Hamm MW, Henderson LM.
Transport and metabolism of pyridoxal and pyridoxal phosphate in the small intestine of the rat.
J Nutr. 1979 Sep;109(9):1542-51. No abstract available.
PMID: 479949 [PubMed - indexed for MEDLINE]

3. Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB.
Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy.
Am J Nephrol. 2007;27(6):605-14. Epub 2007 Sep 6.
PMID: 17823506 [PubMed - indexed for MEDLINE]

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#52 edward

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Posted 23 October 2008 - 08:45 PM

The cheapest and easiest to obtain way to reduce AGE formation would be with pyridoxamine -- the stuff is dirt cheap if you order it pure and in bulk from Asian sources.

First: the cheapest and easiest (not to mention most effective) way to reduce AGE formation would be by practicing Calorie restriction :) .


I'll give you cheapest and most effective (with proper cooking techniques it will also reduce dietary AGEs as you are eating less to begin with).....
but in no way is CR the easiest. In order to do CR right you literally have to weigh most major foods, plug everything into a program like CRONOMETER and track nutrients... not to mention the hunger factor, which maybe is not an issue for some but for me, during my trials of CR, it was. CR especially CRON just seems very impractical, couple that with the amount of muscle loss or lack of ability to maintain any muscle mass, the necessity of a BMI less than 20 which if you are doing it right is where you will be and you have issues making it work in your real life unless you build/structure your life around CR. Throw in the anorexia stigma, looking "unhealthy", energy level issue etc. and there are problems.

Edited by edward, 23 October 2008 - 08:50 PM.





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