Rejuvenation Research, Volume 11, Number 3

The latest issue of Rejuvenation Research is online. You'll find a few more esoteric items on calorie restriction biochemistry, but one paper on methionine restriction is more accessible and interesting. By way of a reminder, recall that there's a fairly good argument for the beneficial effects of calorie restriction to largely stem from lowering the intake of methionine, one of the eight essential amino acids in your diet.

On Methionine Restriction, Suppression of Mitochondrial Dysfunction and Aging

Rats and mice, when subjected to methionine restriction (MetR), may live longer with beneficial changes to their mitochondria. Most explanations of these observations have centered on MetR somehow suppressing the effects of oxygen free radicals.

It is suggested here that MetR's effects on protein metabolism should also be considered when attempting to explain its apparent anti-aging actions. Methionine is the initiating amino acid in mRNA translation. It is proposed that MetR decreases the protein biosynthesis rate due to methionine limitation, which correspondingly decreases generation of ribosomal-mediated error proteins, which then lowers the total abnormal protein load that cellular proteases and chaperone proteins (mitochondrial and cytoplasmic) must deal with.

That's an interesting thought. All cells carry some amount of damaged and malformed proteins as a result of errors in normal operation. The more abnormal proteins, the worse the cell performs - it makes sense that slowing the rate of operation also slows the rate of damage. You can read a little more about that in the context of bacterial reproduction, cell divison, and aging back a way in the Fight Aging! archives. The question is whether this is significant compared to the effects of mitochondrial generation of damaging free radicals.

The other paper that caught my attention is a nice demonstration that the benefits of calorie restriction don't necessarily have anything to do with insulin-like growth factor 1, IGF-1. For those who have been following research into IGF-1 metabolism and aging, a field with at least as much interest as investigations into mitochondria and aging, that might be a counterintuitive result.

Effect of Every Other Day Feeding on Mitochondrial Free Radical Production and Oxidative Stress in Mouse Liver

It is known that dietary restriction (DR) increases maximum longevity in rodents, but the mechanisms involved remain unknown. Among the possible mechanisms, several lines of evidence support the idea that decreases in mitochondrial oxidative stress and in insulin signaling are involved but it is not known if they are interconnected.

It has been reported that when C57BL/6 mice are maintained on an every other day (EOD) feeding their overall food intake is only slightly decreased and plasma insulin-like growth factor (IGF)-1 is even somewhat increased. In spite of this, their maximum longevity is increased, analogously to what occurs in classic DR. Thus, this model dissociates the increase in longevity from the decrease in IGF-1 observed in classic DR.


These results support the possibility that EOD DR increases maximum life span at least in part through decreases in mitochondrial oxidative stress which are independent from insulin/IGF-1-like signaling.

As I said yesterday, metabolism is a complicated affair.


Hi R,

You write fairly often about caloric restriction. I was wondering if you do it yourself, and if so, what has your experience been? I think that would make a great post.



Posted by: Michael G.R. at July 3rd, 2008 7:44 PM

The first rule of Eat Less Club is that you don't talk about Eat Less Club.

Posted by: Reason at July 3rd, 2008 7:56 PM

I recall an early reasonably large scale mortality study relating to milk in that milk was highly corelated to reduced lifespan. This was true of whole or skim milk, so the idea that protein overload could be a problem source makes sense. I wonder if this also is *an* explanation of the benefits of the 7 day adventist vegetarian diet...

Posted by: David Gobel at July 4th, 2008 9:08 AM

Regarding the possibility that reduced protein synthesis is the cause of lifespan extension seen with MetR, well, Matt Kaeberline is trying for the last two years to push the idea that CR is largely mediated by reduced TOR signaling (at least in lower organisms), and he thinks that among the many things that happen when TOR signaling is reduced, the most important one in relation to lifespan extension, is reduced ribosome biosynthesis...

Posted by: Noam at July 4th, 2008 11:34 AM

"I recall an early reasonably large scale mortality study relating to milk in that milk was highly corelated to reduced lifespan."

That is probably true as nature meant for milk to be drunk by calves. On the other hand, a diet emphasizing yogurt does correlate to increased life spans, both in Greece and in the Caucasus mountains.

Posted by: Ed Joyce at July 4th, 2008 12:48 PM

the solution is eating one type of protein per meal.if you eat more than one type lets say egg and fish protein- makes things shoul eat just one protein type per meal.if not body will be acidic.
and not just milk, all cow products are highly antigenic.chees, meat etc.cows are not nessecery for us.totaly useless.

Posted by: Dr, A,Coruhlu at December 22nd, 2008 12:47 PM
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