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 > __________________________________________________ Do You Yahoo!? Talk to your friends online with Yahoo! Messenger. http://im.yahoo.com