82 replies to this topic

[Aphrodite]

See this thread as well http://www.imminst.o...showtopic=26488

[Forever21]

http://www.ncbi.nlm..../pubmed/8429371

Low methionine ingestion by rats extends life span.

Orentreich N, Matias JR, DeFelice A, Zimmerman JA.
Orentreich Foundation for the Advancement of Science, Inc., Biomedical Research Station, Cold Spring-on-Hudson, NY 10516.
Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span.

[HaloTeK]

Forever 21- you nailed this one. What we are to take away from this is that a low methionine diet slows growth. And is probably also one of the main reasons caloric restriction works. Why suffer when we know what stops growth?

I've heard lots of people for years laughing at the puny asian body form -- but their high SHBG prevents too much musculature and promotes long life.

What to take away from this: growth promoting substances take away from maximal longevity-- you want to minimize, but not eliminate methionine sources

I've been saying for years now that growth promoting substances can be a hindrance for longevity. Anyone want some HGH now? <------------ looks are not worth your health

Wonder why IF works? You are definitely limiting methionine in that period, and even if IGF-1 has been proven to rise in people who fast-- if you don't have food in you-- you body doesn't get the signal to grow. <------ hense, helps longevity.

If you are sick-- or really want to speed up protein turnover-- you definitely don't want to practice too much methionine restriction- otherwise, see how it treats you. Episodic periods of growth promoting foods is not a bad idea.

I wonder what the moderate protein paleo eaters think about this-- probably exactly what I think-- that the protein they consume helps lean muscle mass and is great for growth a repair--but may be a bane for maximal longevity. Kitava diet gets better and better. Their diet is low in lectins (mostly tubers, fish, coconut, nuts). Low in methionine and polyunsaturated fats.

Vegetable protein sources are low in methionine- probably what keeps bean eaters alive even with the negatives from a larger lectin intake-- something to think about!!

Edited by HaloTeK, 18 January 2009 - 05:22 AM.

[Forever21]

http://www.sciencedi...4b7443dc6bbff43

The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy

Summary

Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving “aging retardant” effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins – especially those derived from legumes or nuts – tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction – though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

[wydell]

I think that's a good hypothesis regarding muscle growth. \ mass being in contravention to longevity Though does anyone have any thoughts on how one could carry around a decent amount of muscle mass and be on a low methionine or is it simply an impossibility?

I know there are folks practicing calorie restriction but eating a lot of protein powder in the attempt to build \ retain muscle mass. I wonder if they are simply doing themselves in?


If the problem was just simply homocysteine, then one could just take B vitamins and TMG. I guess that action would simply convert excess homocysteine into methionine. And if methionine is the problem and homocysteine is just a symptom, but not the cause of any problem, perhaps that's not going to do any good. Uhh, maybe it might even do harm?

I think I am going to choose to still keep the muscle mass I have. And if I can gain an extra 5lbs muscle mass at 200lbs, I would take that too. I never did want to look like a muscle bound freak, but I don't want to look scrawny either.

Forever 21- you nailed this one. What we are to take away from this is that a low methionine diet slows growth. And is probably also one of the main reasons caloric restriction works. Why suffer when we know what stops growth?

I've heard lots of people for years laughing at the puny asian body form -- but their high SHBG prevents too much musculature and promotes long life.

What to take away from this: growth promoting substances take away from maximal longevity-- you want to minimize, but not eliminate methionine sources

I've been saying for years now that growth promoting substances can be a hindrance for longevity. Anyone want some HGH now? <------------ looks are not worth your health

Wonder why IF works? You are definitely limiting methionine in that period, and even if IGF-1 has been proven to rise in people who fast-- if you don't have food in you-- you body doesn't get the signal to grow. <------ hense, helps longevity.

If you are sick-- or really want to speed up protein turnover-- you definitely don't want to practice too much methionine restriction- otherwise, see how it treats you. Episodic periods of growth promoting foods is not a bad idea.

I wonder what the moderate protein paleo eaters think about this-- probably exactly what I think-- that the protein they consume helps lean muscle mass and is great for growth a repair--but may be a bane for maximal longevity. Kitava diet gets better and better. Their diet is low in lectins (mostly tubers, fish, coconut, nuts). Low in methionine and polyunsaturated fats.

Vegetable protein sources are low in methionine- probably what keeps bean eaters alive even with the negatives from a larger lectin intake-- something to think about!!

[kismet]

I think that's a good hypothesis regarding muscle growth. \ mass being in contravention to longevity Though does anyone have any thoughts on how one could carry around a decent amount of muscle mass and be on a low methionine or is it simply an impossibility?

Looking at the data, I think it's completely impossible on a low methionine diet, maybe on more moderate methionine restriction?

Forever 21- you nailed this one. What we are to take away from this is that a low methionine diet slows growth. And is probably also one of the main reasons caloric restriction works. Why suffer when we know what stops growth?

What do you mean with "why suffer"? How do CRONies suffer as opposed to people doing MR? No, they're not hungry and methionine restriction abolishes growth, so it leads to practically the same suffering: low muscle mass, bone mass, being looked down upon, etc.

Actually it seems more and more as if it is impossible to find a good CR mimetic, because its effects seem tied to slowed growth?

[HaloTeK]

What i usually mean by suffering is trying to eat a very low calorie diet (CR) - or heavily restricting carbs. Methionine restriction seems to allow you to consume more calories (to a point) while allowing for a maximal lifespan. Like I've mentioned before, we need to tweak this to see what is optimal. Growth stages or repair of tissue will be better with higher methionine so this needs closer examining.

[AgeVivo]

There are 2 threads, the other one being http://www.imminst.o...showtopic=26488
I didn't know where to write... answers to your questions are indicated there

does anyone have any thoughts on how one could carry around a decent amount of muscle mass and be on a low methionine or is it simply an impossibility?

- vegetable proteins, especially lentils
- jelly (yes!)
- "met-free" protein powders

Why suffer when we know what stops growth? (...) trying to eat a very low calorie diet (CR) - or heavily restricting carbs

- Doing CR is not obvious indeed (but we are quite confident that it is good if well done)
- Doing MR seems indeed more easy to me (no eggwhites, limited fish/meat, and/or "met-free" protein powders) (evidence is good in rats, otherwise it has been less studied than CR)
- PS: i have in mind that heavily restricting carbs doesn't not in fact extend rodent lifespans. Am i wrong?

a low methionine diet slows growth. And is probably also one of the main reasons caloric restriction works.

probable, as also hinted by kismet; mRNA translation inhibitors, that reduce protein synthesis, extend lifespans of worms. not sure it has been tested in rodents?

[kismet]

What i usually mean by suffering is trying to eat a very low calorie diet (CR) - or heavily restricting carbs. Methionine restriction seems to allow you to consume more calories (to a point) while allowing for a maximal lifespan. Like I've mentioned before, we need to tweak this to see what is optimal.

It's not a suffering if the hunger goes away, that was my point. I've never heard any CR people complain about hunger or suffering. The biggest issue is muscle, bone, strength & comments by other people etc.

I'm pretty disappointed with the way this is shaping up: no near term solution to the issues of CR.

Edited by kismet, 18 January 2009 - 07:41 PM.

[HaloTeK]

[/quote]
It's not a suffering if the hunger goes away, that was my point. I've never heard any CR people complain about hunger or suffering. The biggest issue is muscle, bone, strength & comments by other people etc.

I'm pretty disappointed with the way this is shaping up: no near term solution to the issues of CR.
[/quote]

This is because you need to limit muscle, strength, and hormones to maximize longevity. Also, this is way I think HGH is detrimental(ie, increases muscle mass and hormones).

You are waiting for gene rejuvenation therapy. Right now, you have the trade-off between growth and muscle vs a slight increase in mean longevity. I'll take the happy medium (maintain moderate musculature) - but for theoretical arguments, people need to know why things like CR or methionine restriction helps maximize lifespan. (retards or restricts growth)

[kismet]

Actually I'm pointing out the fallacy of trying to find a miracle CR-mimetic. It won't work.. we'll need to understand the involved downstream pathways (which may or may not increase lifespan independent of growth) and this is nothing else than figuring out metabolism. Biogerontologists have been doing it for years.

I'm a supporter of the growth vs longevity theory for now, it explains why IGF-1 signalling, mTOR and methionine/CR are all involved.

[HaloTeK]

http://www.futurepun...ves/003952.html

Even this points to benefits of methionine reduction automatically from a decrease in total protein intake.

2 years+ and we still haven't really analyzed this (and methionine restriction). I'm very interested in the comments made after the article. Notice how someone comments that a very high fat diet leads to very low IGF-1 <------ if this is the case I may be mistaken about what I think is the optimal carbs vs fat ratio. However, I'm still pritty sure that a higher carb to fat ratio increases SBHG which helps to lower growth. Also, we know that fasting increases IGF-1 <---- but I don't think this marker matters as much when you don't have food in your system to stroke the other hormones. (why you don't see fasting rapidly building up the body). IGF-1 singals might not be as growth promoting as having lower SHBG or higher HGH levels (as in high fat diets).

We need to examine this!

[woly]

Here was an interesting post in sci.life extension today.

Link

The metabolic pathways investigated in the study are a bit over my head but the poster states that with limited polyunsaturated fat intake with increased saturated fat intake, a high methionine diet does not exert atleast some of its harmful effects.

[Aphrodite]

This was posted back in 2007--I remember reading it at the time and not thinking much of it--but with the recent methionine findings, this article describing the benefits of leucine deficiency seems relevant.

http://www.futurepun...ves/004061.html

[Skötkonung]

Hmm, well I better stop taking my methionine powder!
http://www.supplemen...roduct_id=15028

Only kidding!

Regarding muscle mass and methionine, it appears most sports nutrition companies intentionally include methionine in their products. Specifically, whey protein seems to contain quite a bit of the amino acid.

See:
http://www.atlargenu...wheyprotein.php

Casein protein might be a solution for those looking for a low methionine protein source:

The oxidative conversion of casein into protein free of methionine
http://www.jbc.org/c...t/145/2/667.pdf

[Skötkonung]

Some other food for thought:

High-quality life extension by the enzyme peptide methionine sulfoxide reductase
http://www.pnas.org/...5/2748.abstract

Methionine in proteins defends against oxidative stress
http://www.fasebj.or...stract/23/2/464


<h1 id="article-title-1"></h1>

[dubcomesaveme]

High-quality life extension by the enzyme peptide methionine sulfoxide reductase
http://www.pnas.org/...5/2748.abstract

Methionine sulfoxide reductase A and a dietary supplement S-methyl-L-cysteine prevent Parkinson's-like symptoms.
http://www.ncbi.nlm....pubmed/18032652

Here, we show that one member of the MSR family, MSRA, inhibits development of the locomotor and circadian rhythm defects caused by ectopic expression of human alpha-synuclein in the Drosophila nervous system. Furthermore, we demonstrate that one way to enhance the MSRA antioxidant system is dietary supplementation with S-methyl-L-cysteine (SMLC), found abundantly in garlic, cabbage, and turnips. SMLC, a substrate in the catalytic antioxidant system mediated by MSRA, prevents the alpha-synuclein-induced abnormalities. Therefore, interventions focusing on the enzymatic reduction of oxidized methionine catalyzed by MSRA represent a new prevention and therapeutic approach for PD and potentially for other neurodegenerative diseases involving oxidative stress.

[yoyo]

i wonder if "Methionine fasts" would be of benefit.

[stephen_b]

Is there any evidence to for this hypothesis: methionine restriction per se is not what causes the improved lifespans, but sufficient methylation is?

StephenB

[Johan]

Does anyone have any data on how much methionine the average ad lib-eating person typically consumes daily?

[Sillewater]

Should we drink alcohol to lower the absorption of Methionine?

Alcohol and Amino Acid Transport in the Human Small Intestine1

Y. Israel, J. E. Valenzuela, I. Salazar and G. Ugarte
Departments of Biochemistry and Internal Medicine, University of Chile, Santiago, Chile

The effect of ethanol on the absorption of L-methionine was studied in the human small intestine. It was shown that 2% ethanol significantly (P < 0.01) inhibited the absorption of this amino acid by 55%. A 40-g dose of alcohol was given orally to human volunteers as 10 and 20% solutions. Ethanol in the intestinal fluid reached concentrations of 2.5 to 3% and was maintained above 1% for 30 to 60 minutes. The possible significance of these findings is discussed in relation to the nutritional deficiencies that occur in chronic alcoholism in humans.

What I am curious about, is whether is specifically inhibits absorption of methionine or is it because it lowers absorption of all nutrients?

However, to detoxify ethanol we use up methionine:

The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage.

Trimble KC, Molloy AM, Scott JM, Weir DG.
Department of Clinical Medicine, Trinity College, Dublin, Republic of Ireland.
Deficiency of choline and methionine produces hepatic steatosis similar to that seen with ethanol, and supplementation with these lipotropes can prevent ethanol-induced fatty liver. These effects are thought to occur through alterations in membrane phospholipid metabolism, but the mechanism whereby this occurs and the precise nature of the changes brought about by ethanol in the interactions of choline and methionine metabolism remain unclear. Through the known effects on hepatic glutathione (which requires as a precursor a product of methionine catabolism), ethanol might affect hepatic one-carbon metabolism, which requires the participation of both methionine and choline in the transfer of methyl groups. This has been investigated with a radiorespirometric technique to assess the in vivo oxidation of the methyl groups of lipotropes and their intermediates in ethnaol- and control-fed rats. Enzyme activities of one-carbon transfer reactions and the hepatic levels of methionine and alpha-aminobutyrate, an end product of methionine catabolism, have been measured. The effect of ethanol feeding on hepatic S-adenosylmethionine and S-adenosylhomocysteine has also been assessed. Ethanol increases the oxidation to carbon dioxide of the methyl group of methionine by a factor of 2.9 (p = 0.002) and produces a 3.6-fold (p = 0.0001) accumulation of alpha-aminobutyrate, indicating a marked increase in methionine catabolism. Hepatic methionine levels are unchanged by ethanol, however, and this may be explained by a dramatic increase in the turnover of the methyl groups of choline and betaine in response to ethanol (times 3.6 and 4.2, respectively, p < 0.003), suggesting greatly increased use of the choline oxidation pathway to remethylate homocysteine through betaine homocysteine methyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 7691709 [PubMed - indexed for MEDLINE]

Does anybody know if the ethanol would actually work?

Edited by Sillewater, 09 July 2009 - 04:13 AM.

[tunt01]

....dietary supplement S-methyl-L-cysteine prevent Parkinson's-like symptoms.

why can't i find this "S-methyl-L-cysteine" anywhere except specialty chemical vendors ?

[stephen_b]

Should we drink alcohol to lower the absorption of Methionine?

However, to detoxify ethanol we use up methionine

Very interesting find. Methionine seems to be in everything. Now I have a reason to drink a small glass of wine with my eggs in the morning. Hm ... maybe in a coffee mug.

[DrEvil]

However, to detoxify ethanol we use up methionine:

That is why when I went 80% vegetarian I could not metabolise alcohol, could not sleep and had long hangovers. I went to a doc and had my liver tested etc..
mm..
anyhow to get back to the topic.

I posted this on a smilar topic http://www.imminst.o...ion-t24701.html as to why perhaps vegans who would be on a low methionine diet don't reap the benefits of a methionine reduced diets.

HI
Did some search on the internet into vegans and vegetarians. Turns out their homocysteine levels are higher than those of omnivores humans:
http://content.karge...ArtikelNr=12827
click on free abstract link. The reason is Vitamin B 12 deficiency.

One of the benefits believed of methionine restriction is a reduction in the conversion of methionine into homocysteine, which causes oxidative stress ( alzheimers etc.) . Vitamin B12 helps reduce homocystein. Anyhow you guys all know this.
So the reason that methionine restriction does not seem to increase live span in vegans and vegetarians is Vit B12 deficiency.

So this means that methionine restriction combined in humans may well extend life span and maybe more easier to do than calorie restriction !!

...provided you take VitB6,B12 of course.!

[TheFountain]

However, to detoxify ethanol we use up methionine:

That is why when I went 80% vegetarian I could not metabolise alcohol, could not sleep and had long hangovers. I went to a doc and had my liver tested etc..
mm..
anyhow to get back to the topic.

I posted this on a smilar topic http://www.imminst.o...ion-t24701.html as to why perhaps vegans who would be on a low methionine diet don't reap the benefits of a methionine reduced diets.

HI
Did some search on the internet into vegans and vegetarians. Turns out their homocysteine levels are higher than those of omnivores humans:
http://content.karge...ArtikelNr=12827
click on free abstract link. The reason is Vitamin B 12 deficiency.

One of the benefits believed of methionine restriction is a reduction in the conversion of methionine into homocysteine, which causes oxidative stress ( alzheimers etc.) . Vitamin B12 helps reduce homocystein. Anyhow you guys all know this.
So the reason that methionine restriction does not seem to increase live span in vegans and vegetarians is Vit B12 deficiency.

So this means that methionine restriction combined in humans may well extend life span and maybe more easier to do than calorie restriction !!

...provided you take VitB6,B12 of course.!

I hate studies like that which don't adjust for vitamin supplementation. If the 'average' vegetarian or vegan does NOT supplement with essential vitamins and nutrients they are dumb asses. Now if they forced the subjects to refrain from vitamin supplementation that is something altogether different. Either way vegetarianism can be a superior way of living IF proper supplementation is involved. You could very easily control a omnivore study and come up with contrary results based on whatever the hell you wanted to take away or give them during the trial. Then you could say 'meat eaters had more incidences of heart attack because of the cocaine we slipped in their food' or whatever comical variation you wanted to add.

[JLL]

Prior to re-reading this thread I thought it might not be methionine restriction that extends lifespan, but rather limiting any essential amino acid, resulting in reduced protein synthesis. That would explain why protein restriction and methionine restriction both work -- and from what I gather, their LS extension effect is similar. The leucine article hints at this, too.

However, it seems that not only is low methionine good, high methionine is worse than average methionine. And apparently high methionine is worse than, say, high leucine (when other amino acids are kept constant), though I haven't seen much info on this.

I was thinking that it doesn't matter whether you eat a few eggs or a lot of eggs, because you're not going to get MR benefits anyway, but now I'm reconsidering that.

Any updates or new opinions on methionine restriction?

[JLL]

This seems to pinpoint methionine as the bad boy of amino acids:

http://www.mitochond...iction lifespan

Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver.

Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction. In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6-7 weeks, experimental parameters were measured in the liver. Amino acid restriction did not change the levels of the methionine metabolites S-adenosylmethionine and S-adenosylhomocysteine, mitochondrial oxygen consumption and ROS generation, oxidative damage to mtDNA, amounts of the respiratory complexes I-IV, and the mitochondrial biogenesis factors PGC-1alpha and NRF-2. On the other hand, adenylate energy charge, mitochondrial protein oxidation, lipooxidation and glycooxidation, the degree of mitochondrial fatty acid unsaturation, and the amount of the apoptosis inducing factor (AIF) were decreased in the RESTAAS group. Amino acid restriction also increased SIRT1 protein. These results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single aminoacid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification and AIF, and increases SIRT1, in rat liver.

Maybe of interest:

http://www.ncbi.nlm....pubmed/10893413

Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway.

Loss of muscle mass usually characterizes different pathologies (sepsis, cancer, trauma) and also occurs during normal aging. One reason for muscle wasting relates to a decrease in food intake. This study addressed the role of leucine as a regulator of protein breakdown in mouse C2C12 myotubes and aimed to determine which cellular responses regulate the process. Determination of the rate of protein breakdown indicated that leucine is one key regulator of this process in myotubes because starvation for this amino acid is responsible for 30-40% of the total increase generated by total amino acid starvation. Leucine restriction rapidly accelerates the rate of protein breakdown (+11 to 15% (p < 0.001) after 1 h of starvation) in a dose-dependent manner. By using various inhibitors, evidence is provided that acceleration of protein catabolism results mainly from an induction of autophagy, activation of lysosome-dependent proteolysis, without modification of mRNA levels encoding the lysosomal cathepsins B, L, or D. Those results suggest that autophagy is an essential cellular response for increasing protein breakdown in muscle following food deprivation. Induction of autophagy precedes a decrease in global protein synthesis (-20% to -30% (p < 0.001)) that occurs after 3 h of leucine starvation. Inhibition of the mammalian target of rapamycin (mTOR) activity does not abolish the effect of leucine starvation and the level of phosphorylated ribosomal S6 protein is not affected by leucine withdrawal. These latter data provide clear evidence that the mTOR signaling pathway is not involved in the mediation of leucine effects on both protein synthesis and degradation in C2C12 myotubes.

http://grande.nal.us...p;therow=259705

Effect of dietary restriction with and without leucine supplementation on hepatic protein status in rats.

In the present study effect of dietary restriction with and without leucine supplementation was observed on body and liver weights, and liver protein status, in adult rats. Animals were fed on two diets ad lib or were on 50 per cent and 25 per cent intakes. Dietary restriction resulted in loss of body and liver weights, hepatic protein, free-alpha-amino nitrogen and RNA contents and liver cell size (liver weight/DNA ratio). When compared with the control group, the decrease in these parameters was more in the dietary restricted leucine supplemented group. However, hepatic DNA content was not changed with the change in dietary regimen. The results suggest that leucine supplementation with dietary restriction may be more harmful for the animal than dietary restriction alone.

http://www.ncbi.nlm..../pubmed/3784629

Influence of low tryptophan diet on survival and organ growth in mice.

Greater survival and reduced growth were found to characterize mice on a tryptophan deficient diet as compared to fully fed control mice. The 50% survival point was reached by the tryptophan restricted group at 683 days, and by the control group at 616 days. Measurements of body weight, organ weight, and DNA level were made at 8, 12, 24, 36, 52 and 78 weeks of age. Both whole body weight and organ weight of liver, kidney, heart and spleen were about 30% lower in the tryptophan restricted group as compared to the controls, so that the ratio of organ weight to body weight remained at a constant value for both groups. There was no significant change in cell number as determined by DNA measurements, as a result of the tryptophan restriction.

[Blue]

""Methionine sulfoxide reductase A (MsrA) repairs oxidized methionine residues within proteins and may also function as a general antioxidant. Previous reports have suggested that modulation of MsrA in mice and mammalian cell culture can affect the accumulation of oxidized proteins and may regulate resistance to oxidative stress. Thus, under the oxidative stress theory of aging, these results would predict that MsrA regulates the aging process in mammals. We show here that MsrA-/- mice are more susceptible to oxidative stress induced by paraquat. Skin-derived fibroblasts do not express MsrA, but fibroblasts cultured from MsrA-/- mice were, nevertheless, also more susceptible to killing by various oxidative stresses. In contrast to previous reports, we find no evidence for neuromuscular dysfunction in MsrA-/- mice in either young adult or in older animals. Most important, we found no difference between MsrA-/- and control mice in either their median or maximum life span. Thus, our results show that MsrA regulates sensitivity to oxidative stress in mice but has no effect on aging, as determined by life span."
http://www.fasebj.or.../fj.08-127415v1

Very disappointing result. Also makes it more strange how methionine restriction actually achieves lifespan extension.

[JLL]

If someone has access to this paper, PM me.

http://www.ncbi.nlm....ov/pubmed/22255

Long-term tryptophan restriction and aging in the rat.

Growth-retarded rats fed a tryptophan deficient diet at 21 days for periods of 6-22 months were shown to reach normal body weight when subsequently fed Purina Rat Chow. They demonstrated an increased ability over similar aged controls to recover from hypothermia induced by 3-minute whole-body ice water immersion, were able to bear litters at 17--28 months of age, showed a delay in the age of onset of visible tumors, and indicated an increase in their average lifespan at late ages. Animals fed on this diet from 3 months of age revealed a similar ability to reproduce at advanced ages, but not as marked as those placed on the diet earlier. The average lifespan (in months +/- the standard error of the mean) of the rats recovering from the long-term tryptophan-deficient diets was 36.31 +/- 2.26 while the control rats survived an average of 30.5 +/- 1.90 months. The last of 8 rats surviving the period of tryptophan-deficiency died at 45.50 months (1387 days) while the last of 14 control rats died at 41.75 months (1266 days). It is hypothesized that some kind of subtle mechanism exerts its influence on the rats during the period of tryptophan deficiency which caused an accelerated morbidity and mortality as they approached senescence approximately 1 to 2 years after refeeding. This is parallel to the situation with immature animals subjected to long-term caloric restriction and then fed on normal diets.

I'm not sure I understand what the authors means by accelerated morbidity -- didn't the tryptophan-restricted rats outlive the controls?

Edited by JLL, 14 September 2009 - 08:47 PM.

[tunt01]

i'm on the road and dont have my methionine folder w/ me. but i recall reading leucine papers that showed the amino acid was the "key" aminio acid to prevent sarcopenia (ie. protein catabolic state). while the spanish group (author named Barja?) demonstrated that sulfur amino acids (methionine and cysteine) were the primary causes of higher MitROS.

there was a long "methionine restriction=caloric restriction?" debate/thread on this forum, which brought up some of the barja papers. i printed out the entire thread and went through it post by post, line by line. i recall the barja papers having been dismissed by MR (michael rae). i can't recall off the top of my head why he did w/o having the notes w/ me. i read the barja papers and found them pretty interesting and seemed logical to me. the barja group did another follow-up paper to confirm his thesis on MitROS being generated by methionine, which i don't think has been discussed on this forum since the original thread was hashed out.

Edited by prophets, 14 September 2009 - 08:55 PM.