When food becomes limiting, an animal lacking this system would either die of starvation, or produce progeny that die of starvation. In contrast, with this food-sensing system in place, as food declines, the animal begins to build up fat and/or glycogen [the molecular storage form of glucose] reserves, elaborates stress-resistance mechanisms, and delays or suspends reproduction until food is restored. It also activates pathways that extend lifespan, which increases the organism’s chance of being alive and still youthful enough to reproduce if it takes a long time for conditions to improve.

If we accept the evolutionary argument that genetic mechanisms are conserved from simple organisms to humans, then we have at least to contemplate the implications: if a regulatory system as fundamental as that of insulin and IGF is capable of influencing longevity and susceptibility to disease in flies, worms, and mice, then it is likely to do so in humans as well. This research supports the hypothesis that elevations of insulin and IGF will increase the risk of disease and shorten life, and so any diet or lifestyle that elevates insulin and makes IGF more available to the cells and tissues is likely to be detrimental.

To accept these implications at face value, however, we have to be capable of dismissing the conventional wisdom on diet and chronic disease—that an excess of saturated fat, all fat, or perhaps all calories is responsible. Few researchers are willing to take this approach. One who has is Cynthia Kenyon. Once it became clear that the mutations that prolonged longevity in worms were those that reduced the level of activity in the worms’ insulin-IGF pathway, Kenyon began a series of experiments based on a single question: what would happen if she fed worms glucose, in addition to their preferred diet of bacteria? Kenyon added 2 percent glucose to the bacterial medium in which the worms lived, and the lifespan of the worms was reduced by a quarter. Kenyon is still working to establish the nature of this adverse effect of glucose. Her hypothesis: just as mutations increase lifespan in worms by decreasing activity in their insulin-IGF pathway, glucose shortens the lifespan of worms by increasing activity in the same pathway. In October 2004, when Kenyon presented the results of these experiments at a conference on the molecular genetics of aging, she concluded her presentation with a simple, albeit radical question: “Could a low-carb (i.e., low-glycemic-index) diet lengthen lifespan in humans?”