More Evidence For Methionine as the Primary Driver of Calorie Restriction

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You'll recall that experiments restricting intake of the dietary amino acid methionine - without restricting calories - demonstrate some of the same beneficial health effects as calorie restriction. This suggests that the level of methionine ingested is primarily what cues our biochemistry to produce the benefits it does under a low calorie diet that still supplies the right levels of micronutrients. See, for example:

Now here's a reversal of these experiments, in which researchers restrict all the other dietary amino acids except methionine, and come to much the same conclusion:

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.

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[The] 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 amino acid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification [and] increases SIRT1, in rat liver.

Meaning that while methionine restriction accounts for much of calorie restriction, it doesn't account for all of it. There may be multiple parallel mechanisms operating, which in turn suggests that building calorie restriction mimetic drugs that capture anywhere near the entire effect of actual calorie restriction will be challenging. Meanwhile, while research groups are spending hundreds of millions to billions of dollars on research an development, you can obtain the whole benefit of calorie restriction for just about free. Just start eating less, sensibly, while ensuring that your intake of micronutrients remains optimal.