45 replies to this topic

[Gerald W. Gaston]

"Using new techniques developed by Professor Simpson and Professor David Raubenheimer (Auckland) the team showed in the fruit fly that calorie restriction is not responsible for extending lifespan: rather the balance of protein to carbohydrate in the diet was critical"

http://www.scienceal...02-16917-2.html
http://www.usyd.edu....ewsstoryid=2160

[wydell]

Yikes, I am on a quicker path to death according to that theory.


Edit: And it's also going to give all of the calorie restrition folks taking whey to maintain body mass a heart attack. Just kidding, before you take me too seriously.

Edited by wydell, 20 February 2008 - 04:22 AM.

[lunarsolarpower]

Sounds like it may parallel the results of the China Study although I haven't had time to finish reading it yet so I can't say for sure.

[Johan]

I'd like to see some studies on a low-protein diet in mice. Results in fruit flies are kinda hard to translate to humans; mice are much closer "relatives". Many other studies I've heard of have reported increased longevity with more protein (up to a certain limit, I would guess) in various organisms, so it would seem illogical to change one's point of view based on this one study in fruit flies.

Edited by Johan, 20 February 2008 - 10:05 AM.

[Matt]

I agree, basing your diet on a fruit fly is not smart... In rodents it was found that when they were 'zoned' they lived the longest within the CR groups.

[edward]

High Protein, Low Protein, Low Carb, High Carb, High Fat, Low Fat.... It seems like every time I turn around there is a new idea about demonizing one macronutrient or two in favor of the other one or two.

If low protein is the key to life extension, then I too am headed into my grave, which I doubt.

It seems to me that everything boils down to calories and balance and yes I would love to see rat studies on different macronutrient percentages as fruit flies are just way to simple models and come on how much protein does a fruit fly really need, its not like they have muscle mass to maintain.

[inawe]

They did mess around with mice, PMID: 18239565. The mice that ate
lowest percentage of protein got fatter. Hopefully there is more
substantial stuff in the full paper.

[Brainbox]

After doing some research on methionine, that is proposed as supplement in "The Edge Effect" of Braverman (which seems very strange to me), I stumbled upon this review which might be quite interesting in the context of this topic:

Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection.Pamplona R, Barja G.
Department of Basic Medical Sciences, University of Lleida, Lleida 25008, Spain.

Caloric restriction (CR) decreases aging rate and mitochondrial ROS (MitROS) production and oxidative stress in rat postmitotic tissues. Low levels of these parameters are also typical traits of long-lived mammals and birds. However, it is not known what dietary components are responsible for these changes during CR. It was recently observed that 40% protein restriction without strong CR also decreases MitROS generation and oxidative stress. This is interesting because protein restriction also increases maximum longevity (although to a lower extent than CR) and is a much more practicable intervention for humans than CR. Moreover, it was recently found that 80% methionine restriction substituting it for l-glutamate in the diet also decreases MitROS generation in rat liver. Thus, methionine restriction seems to be responsible for the decrease in ROS production observed in caloric restriction. This is interesting because it is known that exactly that procedure of methionine restriction also increases maximum longevity. Moreover, recent data show that methionine levels in tissue proteins negatively correlate with maximum longevity in mammals and birds. All these suggest that lowering of methionine levels is involved in the control of mitochondrial oxidative stress and vertebrate longevity by at least two different mechanisms: decreasing the sensitivity of proteins to oxidative damage, and lowering of the rate of ROS generation at mitochondria.

PMID: 16574059 [PubMed - indexed for MEDLINE]

edit: also refer to the "related links" within PUBMED for some more old and new interesting stuff regarding this.

Edited by brainbox, 04 March 2008 - 03:20 PM.

[rhodan]

From a practical point of view, how to implement an MR diet with real foods and not some laboratory chow ? I mean, without globally restricting total proteins.

Maybe a vegan diet (?), which is hard to implement.

Methionine is important for the synthesis of other important products. Can we compensate the lack of methionine by extra cysteine, taurine, choline, creatine, ... ?

I do not want to prepare my meals enterely from powders

[caston]

Most importantly you want a diet that is tuned to your own genes/proteins and metabolism to increase autophagy.

[rhodan]

Most importantly you want a diet that is tuned to your own genes/proteins and metabolism to increase autophagy.

How do you do that ?

As for autophagy, I do IF (but I will not tinker with lithium, rapamycin, etc )

[caston]

Usually it's due to having less of something i.e protein so the body will consume proteins rather than glycate them.

http://www.plosgenet...95C994E81472CCD

[s123]

From a practical point of view, how to implement an MR diet with real foods and not some laboratory chow ? I mean, without globally restricting total proteins.

Maybe a vegan diet (?), which is hard to implement.

Methionine is important for the synthesis of other important products. Can we compensate the lack of methionine by extra cysteine, taurine, choline, creatine, ... ?

I do not want to prepare my meals enterely from powders

I practice some form of methionine restriction. I also follow a CR diet. I eat 349g tofu (low in methionine) as my main source of proteins. Because tofu is also low in cysteine I take cysteine power. I also use creatine to protect my mitochondria from oxidative stress.

349g of tofu gives you:
0,4g methionine

109g meat (same amount of protein):
0,6g methionine

125g salmon:
0,7g methionine

[s123]

On CRS someone thought that the increase in lifespan of a protein restriction diet could be due to methionine and cysteine restriction.
By reading this I thought about a topic that I had posted here a while ago:

http://www.imminst.o...amp;mode=linear

[rhodan]

I practice some form of methionine restriction. I also follow a CR diet. I eat 349g tofu (low in methionine) as my main source of proteins. Because tofu is also low in cysteine I take cysteine power. I also use creatine to protect my mitochondria from oxidative stress.

If this is your main proteins source, you are severely restricting total proteins (around 25g unless I am incorrect) globally (?)

[s123]

I practice some form of methionine restriction. I also follow a CR diet. I eat 349g tofu (low in methionine) as my main source of proteins. Because tofu is also low in cysteine I take cysteine power. I also use creatine to protect my mitochondria from oxidative stress.

If this is your main proteins source, you are severely restricting total proteins (around 25g unless I am incorrect) globally (?)

Around 70g of protein a day of which 0,9g of methionine a day.

[dannov]

I call bull...shit.

[Brainbox]

I call bull...shit.

Why?

[caston]

I call bull...shit.

Why?

Wouldn't it be ironic and a major blow to the supplement industry if it turned out that in certain cases, depriving cells of nutrients encouraged them to
become leaner and more efficient by selectively cleaning up peroxisomes,cytosolic proteins and mitochondria?

[dannov]

I call bull...shit.

Why?

Brain--

Protein is loaded with amino acids that our cells need to regenerate and rebuild, and provides countless other benefits. I feel that as long as it's a quality source of protein, then it's something that we ought to consume more of--not less. If anything, we ought to consume less wheat products, or none at all.

Then again, maybe I'm reading this wrong...it's referring to protein:carb ratio. I was reading it as "eat less protein." I'm a firm proponent of eating more protein, and less complex carbs.

Edited by dannov, 06 March 2008 - 05:25 PM.

[Shepard]

Wouldn't it be ironic and a major blow to the supplement industry if it turned out that in certain cases, depriving cells of nutrients encouraged them to
become leaner and more efficient by selectively cleaning up peroxisomes,cytosolic proteins and mitochondria?

The supplement industry could do well with it. "Get jacked while eating low protein with HugeJack." There actually was a product a while back that hinted at anabolism in a caloric deficit. It's not made anymore, though.


(I have no clue if HugeJack is an actual product, please no one try to sue me.)

[caston]

Or they could sell products that offer to inhibit transporters (competitive inhibition) for amino acids like met.

Edited by caston, 07 March 2008 - 09:56 AM.

[Mixter]

Although a more general protein restriction may yield more benefits,
it makes a lot of sense to differ between methionine restriction
and restriction of protein rich in the other amino acids.

See: http://groups.google...85c86251ba11d5a

[caston]

I'm trying to understand how restriction or competitive inhibition of a said a amino acid could increase lifespan.

This is one theory.

Perhaps the process could make it more difficult for an unfriendly isoform of the prion protein to occur or for unfriendly prions to replicate. In turn subjects with restriction or inhibition of certain amino acids would have much lower build-up of amyloids.

Edited by caston, 08 March 2008 - 01:39 AM.

[Mixter]

Definitely not elimination from diet, which is not possible for any amino acid.

But there are some pointers why a restriction of methionine may help with life extension,

1) Met increases circulating levels of homocysteine (toxic) and with that, the methylation workload of the organism, and methylation is a key process that declines with increasing age
2) Met shares the AUG sequence with the start codon for all proteins, although I'm not fully sure what this means exactly in terms of restricting methionine yet

I have this news from Life Extension Foundation, who published a reference to a FASEB study two years ago, see below...

http://www.lef.org/w...006_06.htm#mrcr

Methionine restriction = calorie restriction?

The result of research reported in the June, 2006 issue of the FASEB journal revealed that restricting the diet of just one amino acid, in this case, methionine, provided some of the benefits of calorie restriction found among laboratory animals.

Research in rodents has demonstrated that restricting protein, or one of the amino acids that are the building blocks of protein such as tryptophan or methionine, is associated with an increase in longevity. Scientists at the University of Madrid and University of Lleida in Spain hypothesized that this extension of lifespan could be due to a reduction in mitochondrial reactive oxygen species (ROS) generation and oxidative stress, a phenomenon that has been observed during calorie restriction, which is also known to increase lifespan.

In the current study, one group of rats was allowed to eat as much as they wanted of a diet that contained 0.86 percent L-methionine. A second group received the same amount of food each day that the first group consumed the previous day, except the amount of methionine was restricted to 0.17 percent, and L-glutamic acid was increased from 2.7 percent to 3.39 percent for six to seven weeks.

Mitochondria isolated from the heart and liver were examined at the end of the study. It was found that reactive oxygen species production, oxidative damage to DNA, and protein oxidation were all lower in the mitochondria of mice who received the methionine restricted diet compared to the unrestricted group. The changes observed were similar to those revealed in studies of calorie and protein restriction. "This suggests that the decrease in methionine ingestion can be the single molecular component responsible for the decrease in mitochondrial ROS generation and oxidative stress that occurs during calorie restriction, and thus for part of the decrease in aging rate elicited by this dietary manipulation," the authors conclude.

Edited by mixter, 08 March 2008 - 05:55 PM.

[caston]

Definitely not elimination from diet, which is not possible for any amino acid.

If it were possible would you recommend it? Maybe we need some met though or ... ?

e.g. many if not all protein sources contain met but what if you could competively inhibit it so that any met you do consume is neutralised or not transported?

Also if protein restriction increases life span but what does this mean in for consumption of protein disolving enzymes?
If these enzymes break down capsids and reduce inflammation then there should be a positive effect on longevity.

Edited by caston, 12 March 2008 - 03:52 PM.

[s123]

Definitely not elimination from diet, which is not possible for any amino acid.

In the first experiment they did with methionine restriction the mice died because they had given them too little methionine.
Now the established restriction is 80%.

[caston]

Definitely not elimination from diet, which is not possible for any amino acid.

In the first experiment they did with methionine restriction the mice died because they had given them too little methionine.
Now the established restriction is 80%.

Fascinating, do you have a link?

Does it give any suggestions as to why?

[s123]

Definitely not elimination from diet, which is not possible for any amino acid.

In the first experiment they did with methionine restriction the mice died because they had given them too little methionine.
Now the established restriction is 80%.

Fascinating, do you have a link?

Does it give any suggestions as to why?

Methionine is an essential amino acid, you need it to make proteins. Your body can't synthesize it. If you eat too little of it then your body won't be able to make the proteins that contain methionine (or at least not enough of them).

I think that the text about the deaths of the mice isn't available for free on the internet. I will look it up tomorrow.

Interesting article:

Little is known about the biochemical mechanisms responsible for the biological aging process. Our previous results and those of others suggest that one possible mechanism is based on the loss of glutathione (GSH), a multifunctional tripeptide present in high concentrations in nearly all living cells. The recent finding that life-long dietary restriction of the GSH precursor methionine (Met) resulted in increased longevity in rats led us to hypothesize that adaptive changes in Met and GSH metabolism had occurred, leading to enhanced GSH status. To test this, blood and tissue GSH levels were measured at different ages throughout the life span in F344 rats on control or Met-restricted diets. Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001). Liver was apparently the source for this increase as hepatic GSH levels decreased to 40% of controls. Except for a 25% decrease in kidney, GSH was unchanged in other tissues. All changes in GSH occurred as early as 2 months after the start of the diet. Altogether, these results suggest that dramatic adaptations in sulfur amino acid metabolism occur as a result of chronic Met restriction, leading to increases in blood GSH levels and conservation of tissue GSH during aging.

Source: http://www.fasebj.or...tract/8/15/1302

Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.

Source: http://www.blackwell...journalCode=ace

Very good article: http://www.fasebj.or.../full/20/8/1064

Edited by s123, 12 March 2008 - 09:11 PM.

[s123]

I eat 349g tofu (low in methionine) as my main source of proteins. Because tofu is also low in cysteine I take cysteine power.

It seems that taking pure cysteine isn't a good idea after all.

We review here the possible mechanisms of neuronal degeneration caused by L-cysteine, an odd excitotoxin. L-Cysteine lacks the omega carboxyl group required for excitotoxic actions via excitatory amino acid receptors, yet it evokes N-methyl-D-aspartate (NMDA) -like excitotoxic neuronal death and potentiates the Ca2+ influx evoked by NMDA. Both actions are prevented by NMDA antagonists. One target for cysteine effects is thus the NMDA receptor. The following mechanisms are discussed now: (1) possible increase in extracellular glutamate via release or inhibition of uptake/degradation, (2) generation of cysteine -carbamate, a toxic analog of NMDA, (3) generation of toxic oxidized cysteine derivatives, (4) chelation of Zn2+ which blocks the NMDA receptor-ionophore, (5) direct interaction with the NMDA receptor redox site(s), (6) generation of free radicals, and (7) formation of S-nitrosocysteine. In addition to these, we describe another new alternative for cytotoxicity: (8) generation of the neurotoxic catecholamine derivative, 5-S-cysteinyl-3,4-dihydroxyphenylacetate (cysdopac).

http://www.springerl...13384gu6110614/