IT MAY after all be possible to have both a long life and a happy one. Near starvation makes many creatures live longer, but it seems we might be able to get the benefits without having to go hungry.
鈥淐aloric restriction鈥� has been shown to extend the lifespan of almost every animal it鈥檚 been tried on, by up to 50 per cent. A protein called SIR2 may be the key. Yeast given extra copies of the SIR2 gene live longer. And Leonard Guarente of MIT recently showed that SIR2鈥檚 activity depends on the availability of the molecule NAD+, which is used up when we metabolise food. So eating less might slow ageing by making more NAD+ available to the SIR2 protein (快猫短视频, 25 March 2000, p 20).
To put this idea to the test, another team at MIT led by David Sinclair gave yeast extra copies of a gene for the enzyme needed to make or recycle NAD+. One extra copy increased the reproductive lifespan of yeast by 40 per cent on average, they report in the Journal of Biological Chemistry, while four copies increased it by 60 per cent. 鈥淚t鈥檚 exactly what I would have predicted,鈥� says Guarente.
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Surprisingly, the overall levels of NAD+ didn鈥檛 change. The researchers think that what increases is the rate at which it is recycled and thus its availability to SIR2. Guarente isn鈥檛 so sure: he suspects there鈥檚 something wrong with their measurements.
Whatever is going on, the results back the idea that drugs that increase NAD+ production or recycling could extend life by mimicking the effects of caloric restriction. Guarente is already so convinced that he has set up a company called Elixir Pharmaceuticals to try to develop such drugs. He says experiments similar to Sinclair鈥檚 in worms have also succeeded. 鈥淎nd anything that works in both yeast and worms should apply to everything.鈥�
But drugs that affect metabolism in such a fundamental way could have all sorts of side effects. And no one has yet proved that caloric restriction works in any primates, let alone humans. Tests are being carried out on macaque monkeys, but it will be a decade or more before the results are clear.