From: Eugen Leitl (eugen@leitl.org)
Date: Thu Nov 28 2002 - 12:17:59 MST
http://news.bbc.co.uk/1/hi/sci/tech/2521243.stm
Wednesday, 27 November, 2002, 18:34 GMT
Age secrets of little worm
Worm, BBC
C. elegans is found naturally in the soil
By Dr David Whitehouse
BBC News Online science editor
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.
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