If there's one thing that study-of-aging researchers can agree on, it's that caloric restriction seems to prolong lifespan in a number of different organisms. The jury is still out on whether this extends all the way up to humans - people are giving it a try, with varying degrees of dedication and experimental rigor, but it takes quite a while for the results to come in.
One thing that stands out from experiments in small organisms is that cutting back on food intake seems to increase lifespan at the expense of fertility. That makes sense in a sort of three-laws-of-robotics way: the first task is to survive. The second task is to reproduce, as long as that doesn't interfere too much with survival. . .so under very tight energy restrictions, the organism doesn't have enough overhead to move on to the reproduction side of things. (On the other hand, under abundant food conditions, it may be that for some organisms reproduction moves up into first place, depending on what kind of ecological niche they're trying to fill).
This usual thinking here has been that it's total availability of food that throws these switches, through pathways that are sensitive to metabolic flux. There's now a paper out in Nature that makes this model harder to stick with. The researchers look at fruit flies, Drosophila, the very pest that I'm trying to evict from my kitchen at home (thanks to a recent contaminated package of plantains). As it turns out, it's known that these flies don't eat fruit so much as they eat yeast, which accounts for their attraction to bread, vinegar, beer, and overripe produce. This paper tries to pin down which nutrients, exactly, in yeast have effects on fecundity and lifespan, and whether they really are mutually exclusive.
A good way to search for those effects is to take a population of calorically-restricted fruit flies and add nutrients back to their diet to see if anything shows up in lifespan or egg-laying behavior. Vitamins, lipids, and carbohydates were soon ruled out as entire classes - none of the ones found in yeast seemed to have much of an effect either way when they were added back to the diet. That's an interesting result right there - the flies were now getting more food, but their lifespans did not decrease, suggesting that it's not just calories per se that have the effect.
That leaves proteins, and their constituent amino acids. And there things started to get interesting. Adding an amino acid mixture recapitulated the effect of full feeding: lifespans went down, and reproduction went back up. After looking for possible general non-nutritional effects of amino acids (effects on pH, osmotic strength of the food solution, and so on - nothing meaningful found), the team then narrowed things down, trying mixtures of the ten amino acids that are known to be essential for Drosophila versus the ten that aren't. (It's pretty much the same list as for humans, actually).
Adding back the non-essential ones slightly decreased lifespan, with no effect on reproduction. Adding back the essential amino acids (EAAs), though, had substantial effects on both. Now things are getting close to the payoff: amino acids seem to be behind basically all of the caloric restriction effect, and the ten essential ones account for almost all of that. What about looking at them one by one? (I really love science, I have to tell you).
I'll take you right to the end, although plenty of experimentation was needed to get there: it comes down to methionine. Tryptophan has some effect, but methionine alone is sufficient to bring reproduction back to the levels seen in full feeding when you start with calorically restricted flies that are getting the other essential amino acids. It works in a dose-dependent manner, too: if you take restricted-nutrient flies and start putting methionine back into their diet, the fecudity comes up in tandem, eventually plateauing out to a level that you can only raise by giving them more of the other essential amino acids (which are presumably now the things in short supply). That makes it seems as if methionine isn't some signal that it's time to lay eggs - its effects depend on the concentration of the other nine essential amino acids.
Now here's the really neat part: adding methionine back to the diet did not decrease lifespan. So lifespan and reproduction are not always coupled. I'll let the authors lay it out (I've stripped out the references to other papers and to figures that are found in the original text):
Adding back each EAA individually did not decrease lifespan, although, again, methionine alone increased fecundity. Adding back all EAAs except methionine restored lifespan to the level corresponding to dietary restriction, whereas omission of tryptophan had no effect. Notably, restriction of methionine alone also increases lifespan in rodents. Methionine thus acts in combination with one or more other EAAs to shorten lifespan with full feeding. Full feeding thus increases fecundity and decreases lifespan through the effects of different nutrients in Drosophila, the fecundity increase through methionine alone and the lifespan decrease through a combination of methionine and other EAAs. There is thus an imbalance in the ratio of amino acids in yeast relative to the ratio the fly requires for the high fecundity from full feeding, and some consequence of this imbalance decreases lifespan. . .
. . .The mechanisms that influence lifespan are conserved over the large evolutionary distances between invertebrates and mammals, and our results hence imply that in mammals also the benefits of dietary restriction for health and lifespan may be obtained without impaired fecundity and without dietary restriction itself, by a suitable balance of nutrients in the diet.
Now that's going to set off the nutrional supplement industry, for sure, although the lack of effect of vitamins and various lipids will put a crimp into some sections of it. But I find this a fascinating result, and believe that it's probably only the beginning of a long, interesting, and important field of study.