Want to live for ever? Not me. Geneticists, don't mess with my RAS2 and SCH9 genes.

Don't mess with my innocence. Want to live for ever? Nuts. I don’t want to live like that English yew which can live to extreme ages:

http://www.telegraph.co.uk/earth/graphics/2008/01/14/scilive114.jpg

It is tragedy enough that I may live upto 100 years depriving the young nation of its destiny. It is unthinkable that I will ever choose to live upto a thousand. The very thought is disgusting. My function is to discharge the rinams I owe by merely existing. Discharging these rinams is my life. This is my dharma, the controlling phenomenon which holds together many cosmic and social phenomena. Life has to be lived fully and not to be lived like a vegetable or even a stinking yeast or even get stone drunk by eating 1000-year old yeast. “Tests indicated that the dog had a blood alcohol content of 1.6 grams of alcohol per litre of blood. But that was not the result of Dingo having one drink too many, the owner insisted. The hungry pooch had stolen and secretly devoured half a kilogram of fresh yeast dough from the kitchen. Alcohol had formed inside his stomach as a result of the fermentation process, leaving poor old Dingo stone drunk.” http://www.canada.com/edmontonjournal/news/story.html?id=22e44943-7d0c-47ef-b452-8cf4c110f3e2 kalyan 10-fold life span extension reported in simple organism Record longevity for baker's yeast suggests strategies for helping humans live healthier and longer Public release date: 14-Jan-2008 Contact: Carl Marziali marziali@usc.edu 213-219-6347 University of Southern California Biologists have created baker’s yeast capable of living to 800 in yeast years without apparent side effects. The basic but important discovery, achieved through a combination of dietary and genetic changes, brings science closer to controlling the survival and health of the unit of all living systems: the cell. “We’re setting the foundation for reprogramming healthy life,” said study leader Valter Longo of the University of Southern California. The study is scheduled to appear in the Jan. 25 issue of the journal PLOS Genetics. A companion study, showing that the same genetic changes in yeast reverse the course of an accelerated aging syndrome, appears in the Jan. 14 issue of the Journal of Cell Biology. Longo’s group put baker’s yeast on a calorie-restricted diet and knocked out two genes, RAS2 and SCH9, that promote aging in yeast and cancer in humans. “We got a 10-fold life span extension that is, I think, the longest one that has ever been achieved in any organism,” Longo said. In 2005, the same research group reported a five-fold life span extension in the journal Cell. Normal yeast organisms live about a week. “I would say 10-fold is pretty significant,” said Anna McCormick, chief of the genetics and cell biology branch at the National Institute on Aging and Longo’s program officer. The NIA funds such research in the hope of extending healthy life span in humans through the development of drugs that mimic the life-prolonging techniques used by Longo and others, McCormick added. Baker’s yeast is one of the most studied and best understood organisms at the molecular and genetic level. Remarkably in light of its simplicity, yeast has led to the discovery of some of the most important genes and pathways regulating aging and disease in mice and other mammals. A study recently published in Cell (Issue 130, pages 247-258, 2007) reported that a mouse with a gene mutation first identified by Longo’s group lived 30 percent longer than normal and also was protected against heart and bone diseases without apparent side effects. Longo’s group next plans to further investigate life span extension in mice, and also is studying a human population in Ecuador with mutations analogous to those described in yeast. “People with two copies of the mutations have very small stature and other defects,” he said. “We are now identifying the relatives with only one copy of the mutation, who are apparently normal. We hope that they will show a reduced incidence of diseases and an extended life span.” Longo cautioned that, as in the Ecuador case, longevity mutations tend to come with severe growth deficits and other health problems. Finding drugs to extend the human life span without side effects will not be easy, he said. An easier goal, Longo added, would be to use the knowledge gained about life span “in a fairly limited way, to reprogram disease prevention.” In the study appearing in the Jan. 14 Journal of Cell Biology, Longo’s group developed a yeast model for human Werner/Bloom syndromes, incurable diseases that prematurely age, increase cancer incidence and eventually kill their victims. The same mutations that play a central role in the 10-fold life span extension reversed the premature aging process, the researchers found. Longo suggested that although a very simple system was used in his studies, existing drugs targeting analogous anti-aging pathways in humans – specifically the pathway involving Insulin Growth Factor, or IGF-1 – should be considered for testing on Werner/Bloom patients. “Maybe it will do nothing, but having nothing else, I think it’s certainly a good thing to try,” Longo said. In the PLOS Genetics study, Longo’s group identified a major overlap between the genes previously implicated in life span regulation for yeast and mammals and those involved in life span extension under calorie restriction. “We identified three transcription factors … that are very important for the effect of calorie restriction, but at the same time, we also showed that it’s not enough because even without these transcription factors, calorie restriction can still extend life span a little bit,” Longo said. “So that means that we’ve identified a lot of the key players in the calorie restriction effect but not all of them.” Calorie restriction – in practice, controlled starvation – has long been shown to reduce disease and extend life span in species from yeast to mice. Scientists believe that a nutrient shortage kicks organisms into a maintenance mode, enabling them to re-direct energy from growth and reproduction into anti-aging systems until the time they can feed and breed again. Calorie restriction is now being tested by other researchers on primates and even humans, Longo said. Longo has been studying aging at the cellular level for 15 years and has published articles in the nation’s leading scientific journals. His laboratory developed a simple and inexpensive method for measuring the true chronological life span of yeast. Previously, scientists used the number of a yeast cell’s offspring as a proxy for its age. The so-called replicative life span technique remains in use, and the NIA’s McCormick said that Longo’s method was controversial at first. However, she said, the scientific community now appears to accept its usefulness. She said Longo’s “stationary phase” method is particularly applicable to studies of cells that do not divide for most of their life, such as those in the brain or in muscle. “Stationary phase I think of as normal cell survival,” McCormick said. She added that NIA funds both stationary phase and replicative life span research. ### Longo is the Albert L. and Madelyne G. Hanson Family Trust Associate Professor in Gerontology with a joint appointment as associate professor of biological sciences at USC College. A native of Italy, Longo came to the United States to study jazz performance but switched his major to biochemistry as an undergraduate at the University of North Texas. He earned his Ph.D. in biochemistry from UCLA in 1997 and completed his postdoctoral training in neurobiology at USC. The studies were funded by NIA (part of the National Institutes on Health) and the American Federation for Aging Research. USC graduate students Min Wei and Paola Fabrizio were first authors on the PLOS Genetics paper. USC graduate students Federica Madia and Cristina Gattazzo were first authors on the Journal of Cell Biology paper. The other members of Longo’s group were USC graduate students Abdoulaye Galbani, Jesse Smith, Christopher Nguyen, Selina Huey, Lucio Comai, Jia Hu, Huanying Ge and Chao Cheng, USC computational biologist Lei Li, and William Burhans and Martin Weinberger of the Roswell Park Cancer Institute in Buffalo, N.Y. http://www.eurekalert.org/pub_releases/2008-01/uosc-1ls011008.php# How to live forever By Roger Highfield, Science Editor Last Updated: 11:01pm GMT 14/01/2008 New answers to the age old question of how to live for a very long time, even hundreds of years, are given today. One team has achieved a 10 fold extension of life span in a simple organism that has cells very similar to our own. http://www.telegraph.co.uk/earth/graphics/2008/01/14/scilive114.jpg

The English yew can live to extreme ages The scientists at the University of Southern California created baker's yeast - the single -celled organism used in bread making - that is capable of living to 800 in yeast years and without apparent side effects.

This fundamental discovery, achieved through a combination of dietary and genetic changes, brings science closer to controlling the survival and health of the basic unit of all living systems: the cell. "We're setting the foundation for reprogramming healthy life," says Prof Valter Longo, who reports the work in the journal PloS Genetics. "We got a 10-fold life span extension that is, I think, the longest one that has ever been achieved in any organism." Despite its simplicity, yeast has led to the discovery of some of the most important genes and pathways regulating ageing and disease in mice and other mammals. Prof Longo is studying a human population in Ecuador with mutations analogous to those described in yeast, though he cautioned that inheriting longevity mutations from both parents seems to cause severe growth deficits and other health problems. In another study, Dr Patrick Doncaster from the University of Southampton, and Prof Robert Seymour from University College London have found a principle by which some organisms can indefinitely postpone the onset of senescence, the process of deterioration that underpins ageing. They have studied organisms that live to extreme ages, such as the English yew, which defy current evolutionary understanding. One specimen alive today in St Nicholas churchyard near Brockenhurst was recorded in the Domesday Book. Other long lived creatures include a type of Bristlecone Pine which produces viable cones at over 4,000 years of age. Now their secret is revealed in the journal PLoS Computational Biology. 'Our analysis indicates that sedentary organisms, including some types of tree, are particularly likely to achieve this postponement of the onset of senescent ageing,' comments Dr Doncaster. The reason humans and other creatures grow old is, at it simplest, linked with reproduction. Evolution has honed our bodies to produce offspring early in life and spread our genes when we are young, not to wait to a ripe old age, when there is a greater chance of being dead anyway due to disease, accident or misadventure. The yews and other long-lived organisms have found a way to sidestep this by staying still, he says. "We have now answered the question of how they could have evolved from ancestors with senescent life histories. "Young individuals attempting to recruit into the adult population can be "crowded out" by already established adults growing alongside them, favouring a long-slow reproductive strategy.' Could the greying human population crowd out young humans and live longer as a result? Dr Doncaster explains: "Sorry, we've no hope to offer the current human generation. We are considering an evolutionary process, which works over millennia, so we imagine immortality as an evolved endpoint for your n-th generation of descendents. "However, if you care about your reproductive legacy, the secret of immortality is... stay put and outlive your neighbours, then plant your seed in their place." http://www.telegraph.co.uk/earth/main.jhtml?view=DETAILS"grid="xml=/earth/2008/01/14/scilive114.xml

One day we may live till the ripe old age of a 1000 January 15th, 2008 - 12:34 pm Washington, Jan 15 (ANI): Scientists have paved way for helping humans live longer and healthier by creating bakers yeast capable of living up to 800 yeast years without apparent side effects. Since yeasts genes are similar to humans, the findings signify that even humans can have a manifold life extension. The study, led by Valter Longo of the University of Southern California, achieved the important discovery through a combination of dietary and genetic changes. Were setting the foundation for reprogramming healthy life, Longo said. In the study, the researchers put bakers yeast on a calorie-restricted diet and knocked out two genes, RAS2 and SCH9 that promote aging in yeast and cancer in humans. We got a 10-fold life span extension that is, I think, the longest one that has ever been achieved in any organism, Longo said. Anna McCormick, chief of the genetics and cell biology branch at the National Institute on Aging and Longos program officer said: I would say 10-fold is pretty significant. In the study, the scientists identified a major overlap between the genes previously implicated in life span regulation for yeast and mammals and those involved in life span extension under calorie restriction. We identified three transcription factors that are very important for the effect of calorie restriction, but at the same time, we also showed that its not enough because even without these transcription factors, calorie restriction can still extend life span a little bit, Longo said. So that means that weve identified a lot of the key players in the calorie restriction effect but not all of them, he added. Calorie restriction, in practice, controlled starvation, has long been shown to reduce disease and extend life span in species from yeast to mice. Scientists contemplate that a nutrient shortage kicks organisms into a maintenance mode, enabling them to re-direct energy from growth and reproduction into anti-aging systems until the time they can feed and breed again. The study is published in the journal PLOS Genetics. (ANI) 

Calorie restriction-induced life span extension depends on Rim15 and stress response transcription factors downstream of Ras/cAMP/PKA, Tor and Sch9 Min Wei1, Paola Fabrizio1, Hu Jia1, Huanying Ge1, Chao Cheng1, Lei Li1, Valter Longo1¤ 1 University of Southern California, United States of America Calorie restriction, the only non-genetic intervention known to slow aging and extend life span in organisms ranging from yeast to mice, has been linked to the down-regulation of Tor, Akt, and Ras signaling. In this study, we demonstrate that the serine/threonine kinase Rim15 is required for yeast chronological life span extension associated with the deficiencies in Tor and Ras signaling, and show that it is also required for the longevity promoting effect of both extreme (water) and standard (0.5% glucose) calorie restriction. Deletion of stress resistance transcription factors Gis1 and Msn2/4, which are positively regulated by Rim15, also caused a major although not complete reversion of the effect of calorie restriction on life span. Surprisingly, the lack of Rim15 only partially decreased the 10-fold life span extension caused by the combination of CR and the deletion of both RAS2 and SCH9/AKT. These results suggest that Rim15 functions as a central regulator of stress resistance and longevity downstream of the Ras/cAMP/PKA, Tor and Sch9 pathways during calorie restriction. Transcription factors Msn2, Msn4, and Gis1 are also important for Rim15-dependent life span extension but that additional mediators are involved. Editor: Stuart Kim, Stanford University Medical Center, Department of Developmental Biology, Stanford, CA, United States of America Citation: Wei M, Fabrizio P, Jia H, Ge H, Cheng C, et al. (2007) Calorie restriction-induced life span extension depends on Rim15 and stress response transcription factors downstream of Ras/cAMP/PKA, Tor and Sch9. PLoS Genet. In press. doi:10.1371/journal.pgen.0040013.eor Received: September 14, 2007; Accepted: December 10, 2007 Copyright: © 2007 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ¤ To whom correspondence should be addressed. E-mail: vlongo@usc.edu http://genetics.plosjournals.org/perlserv/?request=get-document"doi=10.1371/journal.pgen.0040013.eor"ct=1

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