The week of the rat continues, with a report in Aging Cell that addresses a critical question in dietary restriction studies.

It is known that calorie restriction (the reduction of food intake relative to an ad libitum diet) prolongs lifespan, preserves insulin responsiveness, and confers numerous other benefits in a wide range of animals. It is also known that restriction of methionine in an otherwise ad libitum diet has similar effects: animals live longer than methionine-unrestricted controls, and exhibit a serum hormone profile and visceral fat distribution similar to those of calorie-restricted animals.

Thus it seems that limitation of a single component of the diet confers most of the benefits of limiting the whole diet — or so it would seem, if not for the confounding observation that methionine-restricted animals spontaneously choose to eat less than methionine-unrestricted controls, raising the possibility that the effects of methionine restriction are secondary to overall calorie restriction.

In this clever study by Malloy et al., methionine-unrestricted rats were “pair-fed” the same level of food that methionine-restricted animals eat, and vice versa:

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. … Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction. (emphasis mine) (Link)

One ramification, if these observations prove to be sufficiently general (i.e., “true in primates and specifically H. sapiens), is that in parallel to the more mainstream push toward calorie restriction mimetics, we might also pursue the development of methionine-restriction mimetics. Perhaps there’s even a straightforward way to deplete methionine from regular food, à la the routine pre-digestion of lactose in milk to prevent harm to malabsorbers. (I briefly entertained the idea of inducing methionine malabsorption, but was given pause by the potential side effects. Still, one wonders.)

In the meantime, eat your tofu.