In Methuselah's Mould

T he pathologist makes do with red wine until an effective drug is available, the biochemist discards the bread from her sandwiches, and the mathematician indulges in designer chocolate with a clear conscience. The demographer sticks to vitamin supplements, and while the evolutionary biologist calculates the compensations of celibacy, the population biologist transplants gonads, but so far only those of his laboratory mice. Their common cause is to control and extend the healthy lifespan of humans. They want to cure ageing and the diseases that come with it. " I would take resveratrol if it were feasible, " notes David Sinclair, assistant professor of pathology at Harvard Medical School in Boston, Massachusetts. In the meantime, he adds, " I do enjoy a glass of red wine about once a day. " It was Sinclair's laboratory, in association with a commercial partner, that revealed last August how the team had identifi ed for the fi rst time a group of simple organic molecules capable of extending lifespan. The most profi cient of the group is resveratrol, the plant polyphenol found in red wine, and its discovery as a potential elixir to combat ageing represents another extraordinary advance in a decade of discoveries that have revolutionised the fi eld. Although the life-enhancing effects of Sinclair's polyphenols are so far confi ned to the baker's yeast Saccharomyces cerevisiae, the work suggests that researchers are only one small step from making a giant leap for humankind. " People imagined that it might have been possible, but few people thought that it was going to be possible so quickly to fi nd such things, " says Sinclair. The fi eld of ageing research is buzzing. Resveratrol stimulated a known activator of increased longevity in yeast, the enzyme Sir-2, and thereby extended the organism's lifespan by 70% (Box 1). Sir-2 belongs to a family of proteins with members in higher organisms, including SIR-2.1, an enzyme that regulates lifespan in worms, and SIRT-1, the human enzyme that promotes cell survival (Figure 1). Though researchers still do not know whether SIRT-1, or " Sir-2 in humans, " as Sinclair puts it, has anything to do with longevity, there is a good chance that it does, judging by its pedigree. In any event, resveratrol proved to be a potent activator of the human enzyme. This might not be altogether surprising, at least not now, given that the polyphenol is …