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HarvestingSir2Genes
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http://hubpages.com/hub/Sir2_Gene
"Removal of gene in experimental organisms extends lifespan six-fold
You might have read my article about caloric_restriction (CR), and how its wondrous effect on the lifespan on mice is probably not going to do the same for us humans (as if you were going to forsake cookies, cake and everything else except rabbit food anyway, just to eek out a few more years here on Earth). Well, take heart: recent research has begun to unravel what's gOiNg at a molecular level when an ORGAniSM is starving that makes it live longer.
Research at the University of Southern California, supervised by biomedical gerontologist Valter Longo, focused on two genes in yeasts that typically enjoy longevities of about one week: SCH9 and Sir2. SCH9 controls the cell's processing of food into energy, while Sir2 had already demonstrated some sort of relationship with cell longevity (when it was shortened, yeast cells divided fewer times before dying out; lengthening it created the opposite effect-more cell replications before eventual death). In Longo's research, these two genes were deleted completely from the experimental yeast's chromosome.
The result? The yeast cells (the ones that normally lasted a week) lived to six weeks. The removed genes led the cells to think they were starving, so they switched into ‘starvation mode'. While in starvation_mode, a cell slows growth and development, and becomes more resilient to the type of genetic mistakes that can lead to cancer in later life.
Although human cells share the Sir2 and SCH9 genes with the lowly yeast, naturally, we can't assume what works for a single-celled fungus will work on us. Longo said that he conducted a similar test on human liver cells that confirmed the results, but he's remaining mum on the exact details until his results are published in a peer-review journal.
These findings, of course, don't have any immediate application towards our own efforts to live longer, healthier lives, but future research will focus on genetically replicating the ‘starvation mode' cellular response in us without having to starve. I have a suspicion that resveratrol, a polyphenolic substance in red grapes that is purported to mimic the effects of caloric restriction on longevity, might have some interaction with one or both of these genes (or their effect on the ‘starvation mode'), but confirmation will have to wait until further research is conducted."
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http://www.associatedcontent.com/article/1560015/gene_silencing_and_antiaging.html?singlepage=true
Gene Silencing and Anti-Aging
Live Till 170?
Shedding new light on the biology of aging, researchers recently reported a finding that may explain why a low-calorie diet prolongs healthy life in research animals. With this new insight, scientists may one day develop a drug that would allow humans to live
in good health to the ripe old age of 170.
Scientists base this optimistic prediction on experiments in which laboratory mice live up to 40% longer when fed a nutritionally balanced diet that has 30% less calories than normal. The mice also remain free of age-related disease, although they are less fertile. Similar research with rhesus monkeys has not yet determined if a low-calorie diet has the same effect in primates. But even if caloric restriction can extend human life, very few people could endure such dietary deprivations. Scientists, therefore, hope to develop a drug that mimics the effects of low caloric intake. To create such a drug, one would first have to understand why, at a molecular level, caloric restriction leads to increased longevity.
Research with yeast has now provided that molecular understanding. Yeast are single-celled organisms that are widely used in research and that have many fundamental metabolic pathways similar to those of animals. In the September 22, 2000 issue of Science, Massachusetts Institute of Technology biologist Leonard Guarente reports that his experiments with yeast show that caloric restriction increases longevity by promoting gene silencing.
Gene silencing is one of the many ways to regulate the production of proteins. Genes are sequences of DNA that code for proteins, but if a gene is turned off, or silenced, its protein is not produced. Although some genes are expressed all the time because the cell constantly requires their protein products, other proteins are meant to be present only at certain times during the cell's life cycle. In fact, having the wrong genes activated at the wrong time can damage the cell. Many of the ravages of aging, Guarente says, may be explained by a breakdown of gene silencing.
In his research with yeast, Guarente found that caloric restriction stimulates gene silencing through the SIR2 gene pathway. SIR2 stands for silent information regulator No. 2, and, as the name implies, the SIR2 protein silences other genes. By switching off unwanted genes, SIR2 extends a yeast cell's life span. In Guarente's experiments, a mutant strain of yeast with super-strong SIR2 lived longer than other strains. Similarly, when the SIR2 gene was disrupted in normal yeast, the yeast expired earlier than usual.
Guarente realized the connection between caloric restriction and gene silencing when he discovered that SIR2 requires a cofactor called NAD to effectively turn off genes. A cofactor is a molecule or ion that a protein needs to carry out its cellular work. NAD also plays a vital role in breaking down food, so Guarente hypothesized that the SIR2 protein and metabolic proteins compete for NAD. According to Guarente, when an organism is eating a normal amount of food, most of the NAD in the body is assisting in breaking down this food. Consequently, little NAD is available for SIR2, and gene silencing activity is reduced. Conversely, when an organism has a low caloric intake, more NAD is free to aid SIR2 in silencing genes. This increased gene silencing, in turn, extends longevity by preventing cellular damage from accumulating. Therefore, through the SIR2 pathway, caloric restriction leads to a longer life span.
From an evolutionary perspective, the link between low caloric intake and longer life makes perfect sense, Guarente says. In the wild, during times of food scarcity, it would be advantageous for an animal to put off reproduction until conditions improved; activation of SIR2 and gene silencing provides this advantage by allowing an undernourished animal to live long enough so that it may eventually reproduce.
Guarente hopes that his new insight into aging may one day translate into a drug that activates SIR2 and limits age-related disease. Other biologists are skeptical, however, believing that aging is influenced by many genes and that targeting one gene cannot significantly reduce aging.
Sources
"Searching for Genes to Slow the Hands of Biological Time." Nicholas Wade. New York Times, September 26, 2000, page F1.
"A Pill to Extend Life? Don't Dismiss the Notion Too Quickly." Nicholas Wade. New York Times, September 22, 2000, page A20."
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