Hi Ms. Magnolia: So now we that we know about bread and
mutant worms, what about people? Don'tcha just wonder
sometimes whether these researchers have too much
time/money? Or am I just cranky after being awakened too
early by dystonic leg cramps, not yet having received my
caffeine fix?       Carole

--- janet marie paterson <[log in to unmask]> wrote:
> Gene Yields New Insights Into Why We Age
>
> February 22, 2000 - A gene known to govern the rate of
> aging in yeast cells has been found to be active in mice,
> yielding a new insight into why mice and people age and
> into possible ways of enhancing life span.
>
> The gene's role is to "silence" DNA, meaning it seals off
> suites of genes and prevents the cell from gaining access
> to them.
>
> Since every cell in the human body has the same set of
> DNA instructions, it is essential for each type of cell
> to activate only the genes needed for its own agenda and
> to ignore the rest.
>
> The question of how access to the genes is controlled is
> still mysterious, but it must involve the versatile
> packaging material that clads the DNA, known as chromatin
> because it takes up colored stains.
>
> The new finding, reported in the current issue of the
> journal Nature by Dr. Leonard Guarente and colleagues at
> the Massachusetts Institute of Technology, is that a gene
> first found in yeast cells, a common subject of
> laboratory study, silences the DNA by shaving off a
> certain chemical group from sites along the chromatin.
>
> Loss of the chemicals, known as acetyl groups, makes the
> chromatin bunch up closer to the DNA, blocking access to
> the cell's gene-transcription machinery.
>
> Biologists have long suspected that one of the cell's
> methods for controlling chromatin was adding acetyl
> groups to open the chromatin and removing the groups so
> as to repress the underlying genes. But the protein that
> shaved off the acetyl groups eluded discovery. A leading
> candidate, known as sir2 (for silent information
> regulator No. 2), showed no sign of fulfilling this role
> in test-tube studies.
>
> Now Dr. Guarente has found that sir2 is indeed the cell's
> acetyl group remover, but it needs a special assistant
> that no one had guessed before: a chemical deeply
> involved in the cell's energy metabolism.
>
> "This is an incredible insight," said Dr. C. David Allis,
> a chromatin expert at the University of Virginia. "It
> looks more and more like the cell is tweaking acetylation
> in a forward or backward way to create a balance that
> must be very fundamental to the business of the cell."
>
> The evidence that the sir2 gene may be involved in human
> longevity is indirect. In 1997, Dr. Guarente discovered
> that sir2 controlled the rate of aging in yeast cells.
> When endowed with an extra copy of the sir2 gene, the
> yeast cells lived longer because the gene suppressed
> production of waste genetic material that would clog the
> cell.
>
> This clogging mechanism of aging does not seem to operate
> in mammalian cells. But the sir2 gene occurs in mice and
> humans, and Dr. Guarente believes it may be linked with
> aging in mammals through a different mechanism, one that
> involves its newly found chemical assistant.
>
> The chemical, known as NAD, for nicotinamide adenine
> dinucleotide, is an important intermediate in the cell's
> energy metabolism. NAD is the uncharged form of an
> energy-carrying chemical, and there is probably more of
> it around when the cell is in a state of low energy
> production.
>
> The one intervention that is known to significantly
> prolong the life of laboratory rats and mice is to put
> them on diets with very few calories. No one knows why a
> calorically restricted diet prolongs life.
>
> But Dr. Guarente's theory is that in caloric restriction
> the amount of NAD in cells may increase, spurring the
> activity of its partner sir2. Extra sir2 activity, he
> says, may prolong life in rats and mice just as it does
> in yeast.
>
> "I think it is very interesting work because it provides
> a link between the energetic state of the cell and its
> ability to undergo gene silencing," said Dr. Tomas A.
> Prolla, an expert on the genetics of aging at the
> University of Wisconsin.
>
> Dr. Cynthia Kenyon, who studies aging at the University
> of California at San Francisco, described Dr. Guarente's
> work as a "wonderful hypothesis that should stimulate a
> lot of research."
>
> It is not yet known if caloric restriction -- a diet with
> 30 percent fewer calories but all necessary vitamins and
> minerals -- will also prolong life in humans. Monkey
> studies are under way but are not far enough advanced to
> interpret. Even if it turns out that humans do benefit,
> very few people are likely to be able to maintain such a
> difficult diet.
>
> Dr. Guarente believes there should be a way to reap the
> benefit of caloric restriction without the pain, perhaps
> through a drug that affects the relevant genes, once
> these are discovered.
>
> Is sir2 one of those genes? "I think we have a framework
> now to think about how mammalian aging might occur, and
> this hypothesis frames the next generation of experiments
> we will do," Dr. Guarente said. "And the first has to be,
> 'Can we make animals live longer with sir2?' "
>
> He has engineered both mice and worms with extra copies
> of sir2, and is now measuring their life spans.
>
> Evolutionary biologists have argued that aging is not the
> result of a deliberate genetic program but that it comes
> about as a sort of afterthought because natural selection
> cannot greatly favor genes that benefit an animal after
> the age of reproduction.
>
> Dr. Guarente's assumption that there is such a program,
> and that it may be governed by the same set of genes in
> organisms ranging from yeast to mice to people, butts
> against this theory.
>
> "I'm only a molecular biologist," he said, implying that
> deep evolutionary questions were beyond him. But he
> suggested that it might be useful for evolution to have a
> built-in longevity-controlling program to rely on in
> selecting organisms with life cycles adapted to different
> niches.
>
> Dr. Guarente declined to say if his genetically
> engineered worms were living longer. Another scientist
> said a first batch of worms had lived longer, but had
> received many extra genes besides sir2. Such mutant worms
> can be bought off the shelf, whereas the ones with just
> an extra sir2 gene are a special order.
>
>
> By NICHOLAS WADE
> The New York Times on the Web: Science
>
http://www.nytimes.com/library/national/science/022200hth-aging-genetics.html
>
> janet paterson
> 52 now / 41 dx / 37 onset
> a new voice: http://www.geocities.com/janet313/
> 613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0
>
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