MOST people would not object to living a few years longer than normal, as long as it meant they could live those years in good health. Sadly, the only proven way to extend the lifespan of an animal in this way is to reduce its calorie intake…….’, ‘All you can”t eat

Mar 31st 2005

From The Economist print edition

Even a slight decrease in calories may lead to longer lifespans

MOST people would not object to living a few years longer than normal, as long as it meant they could live those years in good health. Sadly, the only proven way to extend the lifespan of an animal in this way is to reduce its calorie intake. Studies going back to the 1930s have shown that a considerable reduction in consumption (about 50%) can extend the lifespan of everything from dogs to nematode worms by between 30% and 70%. Although humans are neither dogs nor worms, a few people are willing to give the calorie-restricted diet a try in the hope that it might work for them, too. But not manyas the old joke has it, give up the things you enjoy and you may not live longer, but it will sure seem as if you did.

Now, though, work done by Marc Hellerstein and his colleagues at the University of California, Berkeley, suggests that it may be possible to have, as it were, your cake and eat it too. Or, at least, to eat 95% of it. Their study, to be published in the American Journal of PhysiologyEndocrinology and Metabolism, suggests that significant gains in longevity might be made by a mere 5% reduction in calorie intake. The study was done on mice rather than people. But the ubiquity of previous calorie-restriction results suggests the same outcome might well occur in other species, possibly including humans. However, you would have to fast on alternate days.

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Why caloric restriction extends the lifespan of any animal is unclear, but much of the smart money backs the idea that it slows down cell division by denying cells the resources they need to grow and proliferate. One consequence of that slow-down would be to stymie the development of cancerous tumours.

Cancer is the uncontrolled growth of cells. For a cancer to develop efficiently, it needs multiple mutations to accumulate in the DNA of the cell that becomes the tumour”s ancestor. To stop this happening, cells have DNA-repair mechanisms. But if a cell divides before the damage is repaired, the chance of a successful repair is significantly reduced. A slower rate of cell division thus results in a slower accumulation of cancer-causing mutations.

At least, that is the theory. Until now, though, no one has tested whether reduced calorie intake actually does result in slower cell division. Dr Hellerstein and his team were able to do so using heavy water as a chemical marker of the process.

Heavy water is heavy because the hydrogen in it weighs twice as much as ordinary hydrogen (it has a proton and a neutron in its nucleus, instead of just a proton). Chemically, however, it behaves like its lighter relative. This means, among other things, that it gets incorporated into DNA as that molecule doubles in quantity during cell division. So, by putting heavy water in the diets of their mice, the researchers were able to measure how much DNA in the tissues of those animals had been made since the start of the experiment (and by inference how much cell division had taken place), by the simple expedient of extracting the DNA and weighing it.

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Dr Hellerstein first established how much mice eat if allowed to feed as much as they want. Then he set up a group of mice that were allowed to eat only 95% of that amount. In both cases, he used the heavy-water method to monitor cell division. The upshot was that the rate of division in the calorie-restricted mice was 37% lower than that in those mice that could eat as much as they wantedwhich could have a significant effect on the accumulation of cancer-causing mutations.

But calorie-reduction is not all the mice had to endure. They were, in addition, fed only on alternate days: bingeing one day and starving the next. There were two reasons for this. First, bingeing and starving is how many animals tend to feed in the wild. The uncertain food supply means they regularly go through cycles of too much and too little food (it also means that they are often restricted to eating less than they could manage if food were omnipresent). The reasoning here is that metabolic processes evolved in a particular context and might be expected to work best in that context. Replicate the evolutionary context and you might get a better outcome.

The second reason, according to Elaine Hsieh, one of Dr Hellerstein”s colleagues, is that cutting just a few calories overall, but feeding intermittently, may be a more feasible eating pattern for some people to maintain than making small reductions each and every day.

Whether modern man and woman, constantly surrounded by food and advertisements for food, would really be able to forgo eating every other day is debatable. But even if it does work (and Dr Hellerstein has yet to prove that reduced cell division translates into longer life) the temptations of life may prove just too much for wannabe Methuselahs.

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