LONGECITY

Nature 462, 1061-1064 (24 December 2009) | doi:10.1038/nature08619; Received 8 September 2009; Accepted 29 October 2009; Published online 2 December 2009

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila

Richard C. Grandison1,2, Matthew D. W. Piper1,2 & Linda Partridge1

Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, Gower St, London WC1E 6BT, UK
These authors contributed equally to this work.
Correspondence to: Linda Partridge1 Correspondence and requests for materials should be addressed to L.P. (Email: l.partridge AT ucl.ac.uk).

Abstract
Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity1, 2. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature3, 4, 5, 6. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms7, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.


(emphasis mine)
Edited by maxwatt, 27 December 2009 - 05:15 PM.

yes, hence low methionine diet. not atkins/high protein.

and this post:

http://www.imminst.o...&...st&p=371295
Edited by prophets, 27 December 2009 - 07:01 PM.

This is really interesting and doesn't really surprise me personally too much.

Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction.

So now methionine is good for you, but excess protein is not. Hmm.

Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction.

So now methionine is good for you, but excess protein is not. Hmm.

Well, if you are a fruit-fly on a calorie restricted diet, methionine will enable you to reproduce without shortening your lifespan. But for a non-CR fruit-fly, it is not clear from the abstract. But it does suggest that a properly structured non-CR diet can extend lifespan by restricting proteins. This would go against the paleo diet if it were to apply to humans.

Protein restriction, even of just a single essential amino acid, should upregulate autophagy. It would be nice to restrict one that isn't in food we like to eat...

the authors discussed their results in this article which i previous linked

http://www.imminst.o...showtopic=35689 (same study as maxwatt's... discussed)


someone should get their hands on this nature study, it looks more important than i first realized.
Edited by prophets, 28 December 2009 - 08:05 AM.

http://www.nature.co...ure08619-s1.pdf

supplement is here.

Protein restriction, even of just a single essential amino acid, should upregulate autophagy. It would be nice to restrict one that isn't in food we like to eat...

Yeah. Nuts.

(Nuts as a protein source are low in methionine.)

But added methionine for for the flies on CR did not shorten lifespan, but increased fecundity. For flies on normal diet, restricting methionine increased lifespan. Paradoxical.

prophets: Thanks for the links.

from what i can tell, it still all comes down to restricting methionine in-take.

basically they restricted all other essential amino acids, EXCEPT methionine, and this maintained fecundity (reproduction) and life span. But ask yourself this question -- how realistic is it to restrict all other essential amino acids except methionine? it seems totally ludicrous. it's hard enough to restrict methionine alone, meaningfully.

if you look at leucine, isoleucine and other essential amino acids, and their individual impact on the body (ability to inhibit muscle wasting/sarcopenia) etc., it seems more ideal to just restrict methionine and eat the others in plenty. the trade off is obviously your fecundity level.

unless you own a factory to make the exact isocaloric diet and w/ exact nutrient in-take in this study, idk how else to get around it the problem.

the thing that is interesting about the study, is that it is not mutually exclusive per se, but more of a set of co-factors.

from what i can tell, it still all comes down to restricting methionine in-take.

basically they restricted all other essential amino acids, EXCEPT methionine, and this maintained fecundity (reproduction) and life span. But ask yourself this question -- how realistic is it to restrict all other essential amino acids except methionine? it seems totally ludicrous. it's hard enough to restrict methionine alone, meaningfully.

if you look at leucine, isoleucine and other essential amino acids, and their individual impact on the body (ability to inhibit muscle wasting/sarcopenia) etc., it seems more ideal to just restrict methionine and eat the others in plenty. the trade off is obviously your fecundity level.

unless you own a factory to make the exact isocaloric diet and w/ exact nutrient in-take in this study, idk how else to get around it the problem.

the thing that is interesting about the study, is that it is not mutually exclusive per se, but more of a set of co-factors.

A vegan diet, rich in nuts, is perhaps the only 'natural" way to achieve methionine restriction.

from what i can tell, it still all comes down to restricting methionine in-take.

basically they restricted all other essential amino acids, EXCEPT methionine, and this maintained fecundity (reproduction) and life span. But ask yourself this question -- how realistic is it to restrict all other essential amino acids except methionine? it seems totally ludicrous. it's hard enough to restrict methionine alone, meaningfully.

if you look at leucine, isoleucine and other essential amino acids, and their individual impact on the body (ability to inhibit muscle wasting/sarcopenia) etc., it seems more ideal to just restrict methionine and eat the others in plenty. the trade off is obviously your fecundity level.

Well, these are flies, so it's hard to say how fly fecundity or any of the rest of it translates to humans, if at all. However, they didn't show that methionine was the only key to enhanced longevity. They did show that adding all the essential AAs shortened lifespan a lot, which might make us think twice about high protein diets, at least if the same effect is seen in mammals. Unfortunately, they didn't do the experiment where one essential AA was left at CR levels, while others were increased. I contend that restriction of any essential AA will enhance longevity, although without running the experiment, I can't comment on the degree of longevity enhancement. I really don't want to restrict methionine. It restricts food choices too much. I'd rather find an essential AA that doesn't seem to be critical to some faculty that is important to me and is actually easy to restrict. I have a feeling that animal products are going to be high in all the essential AAs, so maybe this scheme is doomed from the start.

A vegan diet, rich in nuts, is perhaps the only 'natural" way to achieve methionine restriction.

its quasi my diet ATM. main sources of protein are whey protein, beans, nuts. i do eat animal sourced protein a couple times a week, in small portions.

Seems like we are facing tradeoffs with this approach. The ones none of us really would leke to do on the long run (at least I wouldn't..). Sarcopenia and being sexually "muted" doesn't seem like a nice scenario at all.. I wonder if there's still some chance to find a way to have the benefits of CR (or AR - Amino acids restriction) without actually doing it (forcing/fooling organism to keep the repair/maintenance rate/state we are striving for).
Edited by VidX, 29 December 2009 - 08:47 AM.

A vegan diet, rich in nuts, is perhaps the only 'natural" way to achieve methionine restriction.

its quasi my diet ATM. main sources of protein are whey protein, beans, nuts. i do eat animal sourced protein a couple times a week, in small portions.

Are you concerned about the high level of n-6 fatty acids in nuts, or lectins in beans? I have a raw cashew habit myself, (they're great with dark chocolate) but the n-6 problem makes me try to keep it at the level of a small snack rather than a significant protein source.

Are you concerned about the high level of n-6 fatty acids in nuts, or lectins in beans? I have a raw cashew habit myself, (they're great with dark chocolate) but the n-6 problem makes me try to keep it at the level of a small snack rather than a significant protein source.

my comments probably overstated my actual nut intake. i eat nuts every day, but it's like 7 almonds, 7 walnuts ontop of oatmeal, etc. the real protein is from whey.

If the methionine data keeps coming in support of restriction=longevity, perhaps there is a market for low methionine whey protein, if it is economically feasible to separate.

I contend that restriction of any essential AA will enhance longevity

This is my suspicion as well. It would make sense given the seemingly paradoxical results, at least. I think I posted a couple of studies in another thread suggesting that reducing other AAs might increase lifespan.

So what is the exact theory here - restricting Amino Acids forces the body to upregulate autophagy in order to make up for the dietary deficit? In essence, the body has to break down or recycle tissue/muscle in order to fulfill its need for essential AAs. As far as increased autophagy has been linked to life extension I suppose this is a good thing, however, it seems to be a bit dangerous as a long term strategy if you do not consistently get the proper/necessary amounts of AAs.