Science
Ageing cells
Bernard Dixon
Do we grow old by mistake? One currently Popular theory of ageing strongly suggests so — the mistake involved being a particular type of error in the body's cellular machinery. When we are young, the intricate chemical processes in our cells proceed efficiently and faultlessly, but gradually, it seems, fundamental mistakes develop. Cells, and the body itself, can tolerate occasional errors of this sort but eventually the mistakes accumulate and impair the normal functions of the various tissues.
This account of ageing was first expounded nine years ago by Dr Leslie Orgel. Since then more and more supporting evidence has been assembled — much of it by Dr Robin Holliday's research group at the National Institute for Medical Research, Mill Hill, London. Convincing data now suggest that Orgel's theory holds good in fungi — in which most of the experiments have been conducted — and in recent months reports from Mill Hill have indicated that it probably explains ageing in human cells too.
To understand this evidence, we must consider in more detail the type of mistake thought to occur in ageing cells. The behaviour of any cell — whether in the brain, skin, liver, or any other part of the body — is determined by a genetic blueprint which resides in the DNA in the cell's nucleus. DNA is a long, complex molecule which carries, encoded in a sequence of chemical groupings along its length, instructions for all the chemical reactions conducted by that particular cell. When the cell multiplies by division, the DNA replicates accurately and precisely, carrying the same coded instructions into the two daughter cells.
The genetic instructions are made manifest in the form of proteins. Some of these form part of the structure of the cell; most function as proteins — catalysts which promote specific chemical reactions. It is the portfolio of enzymes and other proteins which distinguish, say, a kidney cell, performing its role in disposing of the body's waste materials, from a cell in the pancreas whose function is to produce insulin. Clearly, accurate copying of the coded information carried by DNA is vital. Should anything go amiss, the end result is likely to be a faulty enzyme — one unable to perform its task properly in the economy of the cell.
Such 'translation errors' form the crux of Orgel's theory. They happen at random he suggests, leading to the assembly of defective enzymes and other proteins. Because proteins are, like DNA molecules, comparatively large and complicated, the occasional tiny error may not matter. But gradually the defects accumulate. Consequently more and more of the cell's vital chemistry works inefficiently. Eventually — in fungi at least — there is an error catastrophe,' which coincides with death.
The most recent report from Mill Hill was a paper published in Nature (vol 239, p 316) last week by Dr C. M. Lewis and Dr G. M Tarrant, who have been seeking evidence of defective enzyme formation during the ageing of a particular type of human lung cell. Their results were very suggestive. They used two methods to measure a single enzyme in the lung cells at different times during ageing. One analysis revealed the amount of enzyme present. The other showed the enzyme's activity in catalysing its characteristic reaction. One would normally expect the two measurements to coincide. Lewis and Tarrant found, however, that though enzyme activity declined, the amount of enzyme did not fall accordingly.
This is precisely what Orgel's theory predicts — the enzyme continued to be produced but it was faulty and thus not as active as before. There is still far to go in relating this work to human ageing, but for my money Orgel's hypothesis (which has already withstood the test of time and led to verifiable and verified predictions) provides one of the most intellectually satisfying explanations of ageing to be found among the many rival theories now jostling for acceptance.
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