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Wednesday, 27 November, 2002, 18:34 GMT
Age secrets of little worm
Worm, BBC
C. elegans is found naturally in the soil

New research suggests that changes in less than 1% of our genes are responsible for the ageing process.

Work carried out on nematode worms shows that only a very small number of genes become less efficient as our cells get older.

These genes produce proteins that keep the cells working properly and protect them against stress.

But when they fail, the effects can be devastating and this helps explain, on a molecular level, why our bodies wither.

Lifetime of stress

Nobody really knows why we get older. Some scientists argue that after an organism passes reproductive age its use to future generations is limited and it just slowly fades away.

Other scientists can describe in broad terms how an organism changes as it gets older, but what actually happens to the organism's cells to cause them to behave this way is far from clear.

There are several theories of which the most popular is that as they age, cells become less efficient and less able to rid themselves of waste and toxic products. Eventually, they are no longer able to work at all - and die.

According to James Lund, of Stanford University Medical Center, US, and colleagues, reporting in the journal Current Biology, "ageing can be thought of as a result of a lifetime of stress and hence genes that are regulated by stress could show age-dependent changes".

To look for these possible changes in the genes as an organism gets older, the research team grew batches of the well-studied nematode worm C. elegans. This was the first animal to have its genome decoded by science in 1998.

Significant find

The worms were allowed to develop to one of six specified ages between three days and 19 days, beyond which few of the organisms would normally survive.

Genetic material was then extracted from the nematodes' cells and placed on DNA microarray chips. These devices were able to check which of the creatures' 19,626 currently identified genes were active and at what stages during their lives.

The scan showed that over the course of a worm's life, 201 genes changed their pattern of activity.

The researchers then divided the 201 genes into two groups. The first included genes that changed when the worm was young but showed a constant activity later. The other group included genes that changed in the organism's later life.

There were 164 genes in the second category. And, of interest to the researchers, this collection included two so-called stress genes - sometimes called heat-shock genes.

It was an important observation, says the team, because there are only 26 known heat-shock genes in the worm's genome. To find two in the group of 126 is highly significant, it believes.

Age test

Proteins made by heat-shock genes have an important role in folding and shaping other proteins which is essential to their proper function.

If the heat-shock proteins do not work properly, there could be an accumulation of malformed, harmful proteins inside a cell that would impair its function and cause it to age.

Another suggestion given for why cells age is that they become damaged by so-called free-radicals - highly reactive molecules that can initiate a range of undesirable chemical reactions.

However, the researchers found no evidence to support this theory among the genes that change as C. elegans ages.

The observation that a relatively small number of genes change over the worm's lifetime is consistent, say the researchers, with the idea that ageing is caused by molecular damage that accumulates in the cells until they - and the organism - dies.

Detailed knowledge obtained by probing these genes may provide the basis for a molecular test to determine the age of cells.

It could also allow for future experiments that interfere with the age-related genes to see if the lifespan of cells can be increased.

See also:

18 Feb 02 | Boston 2002
10 Dec 98 | Science/Nature
29 Oct 02 | Science/Nature
31 Aug 00 | Science/Nature
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