Here is the outline of an interesting experiment:

• take a group of ordinary people and start them on the practice of calorie restriction (CR)
• extract serum from the participants' blood plasma before starting and after some months of CR
• culture cells on both sets of serum and examine the differences in biochemistry

You'll find that the CALERIE study research teams have done just this. The abstract is at PubMed:

Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals.

Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period).

Cells cultured in serum from ADF participants showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels.

This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity.

As of late 2008, I'd guesstimate that something in the order of one to two billion dollars have been invested into developing drugs that will produce some fraction of the effects of calorie restriction on mammalian biochemistry - such as increasing the expression of Sirt1. Most people can get these benefits for free, however, by simply eating a less calorie-packed diet. You should look into it - calorie restriction isn't anywhere near as hard as those who have never tried it make it out to be.

Posted by Reason at September 16, 2008 7:44 PM | TrackBack (0)