Finally, the benefits of caloric restriction are assumed to have evolved as a strategy for switching resources between reproduction and tissue maintenance. Such a mechanism would greatly help an organism ride out successive waves of feast and famine. That would explain why mice on caloric restriction generally become infertile.

So it is somewhat puzzling that the fat mice fed resveratrol by Sinclair showed no decline in fertility. Nor have a group of female rhesus monkeys who have been eating a reduced-calorie diet since 1987, scientists at the National Institute on Aging reported recently. If there’s no trade-off between longevity and fertility, the theory of the evolution of caloric restriction could be wrong or incomplete.

The road to the discovery of the first SIRT-type gene began in 1991 when two graduate students at MIT asked Guarente if they could join his laboratory to study ageing. They were Brian Kennedy, now at the University of Washington, and Nicanor Austriaco, now a Dominican priest who teaches biology and theology at Providence College in Rhode Island.

Guarente said his students could have a year to search for genes that might affect aging in yeast. In the event, they took four years just to find a strain of yeast that lived longer than others. A gene called sir-2, for silent information regulator-2, turned out to be responsible for this longevity effect.

The lab was then joined by Sinclair, who figured out the unusual mechanism by which sir-2 repressed aging in yeast. Guarente then found the gene is activated by a common chemical that reflects the level of metabolism in a cell. He proposed sir-2 and its counterpart genes in animals were the mediators of caloric restriction: the genes sense when the body is running low on nutrients and direct a wide range of metabolic adjustments, from preserving tissues to burning off fat reserves.

... contd.