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  1. leadcoffin
    http://news.aol.com/health/article/...l/112074?icid=100214839x1206835873x1200362792

    Scientists Create 'Exercise in a Pill'

    By MALCOLM RITTER
    ,
    AP
    posted: 3 DAYS 14 HOURS AGO
    NEW YORK (July 31) - Here's a couch potato's dream: What if a drug could help you gain some of the benefits of exercise without working up a sweat? Scientists reported Thursday that there is such a drug - if you happen to be a mouse.
    1217541094695.JPEG Salk Institute / AP
    Ron Evans, of the Salk Institute for Biological Studies, holds a vial of a drug that he says chemically mimics exercise.



    Sedentary mice that took the drug for four weeks burned more calories and had less fat than untreated mice. And when tested on a treadmill, they could run about 44 percent farther and 23 percent longer than untreated mice.
    Just how well those results might translate to people is an open question. But someday, researchers say, such a drug might help treat obesity, diabetes and people with medical conditions that keep them from exercising.
    "We have exercise in a pill," said Ron Evans, an author of the study. "With no exercise, you can take a drug and chemically mimic it."
    Evans, of the Salk Institute for Biological Studies in La Jolla, Calif., and the Howard Hughes Medical Institute reports the work with colleagues in a paper published online Thursday by the journal Cell.
    They also report that in mice that did exercise training, a second drug made their workout much more effective at boosting endurance. After a month of taking that drug and exercising, mice could run 68 percent longer and 70 percent farther than other mice that exercised but didn't get the drug.
    Both drugs have been studied by researchers for other uses. The no-exercise drug is in advanced human testing to see if it can prevent a complication of heart bypass surgery.
    Evans noted the drugs might prove irresistible for professional athletes who seek an illegal edge. He said his team has developed detection tests for use by the World Anti-Doping Agency. Evans said he has no financial interest in either drug or the test.

    Resveratrol, a substance being studied for anti-aging effects, has also been reported to enable mice to run farther before exhaustion without exercise training. But the drugs in the new study appear to act more specifically on a process in muscles that boosts endurance, the researchers said.
    Still, it takes more than just altered muscles to turn a sedentary mouse into a distance runner, Evans said, and "honestly, I just don't know how that happens. Whether it would happen in a person, I don't know. I think it's a small miracle it happened at all."
    In fact, Evans said that when the experiment with sedentary mice was suggested by an outside scientist who was reviewing the lab's research, "I didn't think it was going to work."
    The no-exercise drug is called AICAR. Previous experiments suggest that it might protect against gaining weight on a high-fat diet, which might make it useful for treating obesity, Evans said. But it would have to be taken for a long time, he said, so its safety in people would have to be assured.
    Experts who study muscle agreed that a drug like AICAR may prove useful someday in treating obesity and diabetes. Many drug companies are working on such drugs in diabetes because in animals, AICAR stimulates muscles to remove sugar from the blood, noted Laurie Goodyear of the Joslin Diabetes Center in Boston.
    People who can't exercise because of a medical condition like joint pain or heart failure might also benefit from such a drug, experts said.
    But Eric Hoffman of the Children's National Medical Center in Washington, D.C., noted that AICAR mimics only aerobic exercise, not the strength training that might be more useful to bedridden people or the elderly, for example. He also cautioned that it's not clear whether the new mouse results can be reproduced in people.
    Goodyear said exercise has such widespread benefits in the body that she doubts any one pill will ever be able to supply all of them. "For the majority of people," she said, "it would be better to do exercise than to take a pill."

    Copyright 2008 The Associated Press. The information contained in the AP news report may not be published, broadcast, rewritten or otherwise distributed without the prior written authority of The Associated Press. Active hyperlinks have been inserted by AOL.

    2008-07-31 12:09:14


    My new aspiration in life is to become a test subject for further research of this amazing new substance.

Comments

  1. fnord
    And here come s the first wave of super soldiers...
  2. sylenth
    now that is some evolutionary research going on. this one will be a top charter for the home infommercials.
  3. Heretic.Ape.
    finally i can cross "start exercising" off of my to-do list
  4. leadcoffin
    A more science-heavy article

    Researchers Identify Drugs that Enhance Exercise Endurance

    Researchers have identified two drugs that mimic many of the physiological effects of exercise. The drugs increase the ability of cells to burn fat and are the first compounds that have been shown to enhance exercise endurance.

    The video shows two mice exercising on treadmills in the lab of HHMI researcher Ronald Evans. The mouse on the right has received one of the two drugs tested, while the mouse on the left is a wild-type mouse that has not received any drug.

    Video: Courtesy of the Laboratory of Ronald Evans/HHMI, Salk Institute

    Both drugs can be given orally and work by genetically reprogramming muscle fibers so they use energy better and contract repeatedly without fatigue. In laboratory experiments, mice taking the drugs ran faster and longer than normal mice on treadmill tests. Animals that were given AICAR, one of the two drugs, ran 44 percent longer than untreated animals. The second compound, GW1516, had a more dramatic impact on endurance, but only when combined with exercise.
    [​IMG]
    “This is a drug that is like pharmacological exercise.”
    Ronald M. Evans [​IMG]
    Ronald M. Evans, the Howard Hughes Medical Institute investigator who led the study, said drugs that mimic exercise could offer potent protection against obesity and related metabolic disorders. They could also help counter the effects of devastating muscle-wasting diseases like muscular dystrophy. Evans and his colleagues, who are at the Salk Institute for Biological Studies, published their findings on July 31, 2008, in an advance online publication in the journal Cell.
    Concerned about the potential for abuse of the two performance-enhancing drugs, Evans has also developed a test to detect the substances in the blood and urine of athletes who may be looking for way to gain an edge on the competition.
    In 2004, Evans and his colleagues genetically engineered mice that had altered muscle composition and enough physical endurance to run twice as far as normal mice. These “marathon mice” had an innate resistance to weight gain, even when fed a high-fat diet. “We made these mice and they had low blood sugar, they resisted weight gain, they had low fats in their blood. They were much healthier animals,” Evans said. “And when we put them on a treadmill, the engineered mice ran twice as far than normal mice - they transformed into remarkable runners.”
    The scientists achieved these effects by modifying a gene called PPAR-delta, a master regulator of numerous genes. Evans and his colleagues showed that by enhancing PPAR-delta's activity, they had shifted the genetic network in muscle cells to favor burning fat over sugar as their energy source. But the effects seen in the marathon mice were caused by a genetic manipulation that was present in their bodies as their muscles were developing. Evans's group began to wonder whether they could duplicate these effects by turning on PPAR-delta in adult mice.
    “We had shown that we could pre-program muscle using genetic engineering. If you express this gene while the muscle is being formed, you can increase the amount of non-fatiguing muscle fibers,” Evans says. “But what about reprogramming in an adult? When all the muscles are in place, can you give a drug that washes over the muscle for a few hours at a time and reprograms existing muscle fibers? That's a very different question.”
    PPAR-delta has long been an attractive drug target because of its central role in metabolism, so Evans and his colleagues had no shortage of chemical compounds available to test. They began by testing a compound called GW1516. They treated young adult mice with the drug for five weeks. “We measured gene changes and the muscles looked like they were responding, so we knew the drug was working.”
    Thus, while fully expecting the drug to dramatically increase endurance - Evans says, “There was no change at all in running performance. Nothing — not even a percent.”
    Surprised by this spectacular failure, Evans and his colleagues decided to try a different approach, based on real-life experience. “If you're out of shape - and most of us are - and you want to change, you have to do some exercise. The way we reprogram muscle in adults is by training.”
    So the scientists subjected two groups of mice — one that received the drug and one that did not — to interval training. The mice ran for 30 minutes on a slow treadmill five days a week for a total of four weeks. At the end of the training period, all of the mice - regardless of whether they had received GW1516 - had improved their performance. Those that had received GW1516, however, ran 68 percent longer than those that had only done the exercise training. “The dramatic effect of the drug was stunning,” Evans said.
    The scientists were intrigued by this synergistic interaction and wanted to know how exercise allowed the drug to work. One possibility was an enzyme called AMP kinase (AMPK). During exercise, cells burn ATP as their primary source of energy. In the process, they create a by-product called AMP. When cells sense the presence of AMP, they activate AMPK. Activation of AMPK creates more ATP for the cell to burn. AMPK also triggers changes that lower blood sugar, sensitize cells to insulin, enable cells to burn more fat, suppress inflammation, and otherwise influence metabolic pathways. This is one reason that exercise is so beneficial.
    Evans's team found that in addition to replenishing the cell's energy stores, AMPK also assists PPAR-delta in activating its gene targets. “It hops onto PPAR-delta in the nucleus and turbo-charges its transcriptional activity,” Evans explained. “We think AMPK activity is the secret to allowing PPAR-delta drugs to work.”
    The critical question was whether chemical activation of AMPK is sufficient to trick the muscle into thinking it has been exercised. The second drug, called AICAR, enabled them to answer that question. AICAR mimics AMP, Evans said, “so muscle thinks it's burning fat.” The researchers were encouraged when they found that when they gave the drug to mice, they activated many of the genes in muscle that are turned on by exercise.
    After four weeks of treatment with AICAR, Evans and his colleagues once again challenged sedentary mice to run on the treadmill. They found that mice that had received AICAR were able to run 44 percent longer than untreated mice. “This is a drug that is like pharmacological exercise,” Evans says. “After four weeks of receiving the drug, the mice were behaving as if they'd been exercised.” In fact, he says, those that got the drug actually ran longer and further than animals that received exercise training.
    The animals receiving AICAR improved their running performance and their ability to burn fat. None of these effects, however, were as strong as they were in the animals that received both exercise and activation of PPAR-delta via GW1516.
    Evans said this indicates that the benefits are likely due to collaboration between cells' AMPK and PPAR-delta signaling pathways. The team's genetic analyses supported this hypothesis; they found that the drugs alone activated a subset of exercise-induced genes, but activating both pathways (by combining GW1516 with exercise) activated a larger group of genes. Many of those genes regulate metabolism and muscle remodeling. Evans and his colleagues called this the “endurance gene signature.”
    Like exercise, the two drugs trigger a variety of changes that contribute to muscles cells' improved endurance and ability to burn fat. These changes include an increase in mitochondria, the structures responsible for producing energy; a shift in metabolism that takes advantage of lipids as an energy source; and an increase in blood flow, which enables the steady delivery of fat to burn. While the scientists only examined the drugs' effects on muscle cells in this study, Evans says it is likely that they confer benefits on other systems impacted by exercise, such as the heart and lungs.
    Based on his group's findings, Evans is optimistic about using small molecules that mimic exercise to treat and prevent a variety of common conditions. For example, the way in which the drugs transformed the muscle fibers of mice suggests they might help reverse the muscle frailty associated with aging or diseases like muscular dystrophy. “We have now created the potential for a really simple intervention in an area of major health problems for which there is no intervention,” he says.
    More broadly, the drugs could offer the benefits of exercise to people who do not get enough. “Almost no one gets the recommended 40 minutes to an hour per day of exercise,” he says. “For this group of people, if there was a way to mimic exercise, it would make the quality of exercise that they do much more efficient. This might be enough to move people out of the `danger zone' toward a lower risk, healthier set point. By intervening early, you may forestall the emergence of more serious problems.”
    Evans expects these types of drugs will be attractive to a variety of individuals. “If you like exercise, you like the idea of getting more bang for your buck,” he says of GW1516. “If you don't like exercise, you love the idea of getting the benefits from a pill,” as with AICAR. So, while Evans sees tremendous opportunities for health benefits from drugs that mimic exercise, he also sees serious potential for abuse.
    “Drugs that improve health are not only going to be used by people who have medical problems. They may also be used by people who are healthy - or by athletes who want an edge,” said Evans. He noted that the sports world has long been aware of his lab's work demonstrating a link between PPAR-delta and endurance. What's more, GW1516 has a relatively simple chemical structure and can be synthesized easily. Evans anticipates that athletes will seek their own sources of the drug - if they haven't already.
    Concerned about the potential for abuse, Evans thought it was important to develop a test that could detect whether the drug was being used as a performance-enhancing substance. With HHMI support, his group has created a highly sensitive test that uses mass spectrometry to detect the two drugs and their metabolic by-products in the blood or urine. While the test is very reliable in mice, Evans says that further analyses are needed to ensure that it is accurate in humans. Evans, HHMI and the World Anti-Doping Agency are now working to certify the detection system and make it available in time to retroactively test athletes who compete in the 2008 Olympics.

    [​IMG][​IMG] [​IMG][​IMG][​IMG]MORE HEADLINES
    [​IMG][​IMG]

    leadcoffin added 0 Minutes and 38 Seconds later...

    http://www.hhmi.org/news/evans20080731.html
  5. Nature Boy
    I'm confused here. How can it be a "no excercise" drug when its benefits are only derived from the increased desire to excercise that it produces? Regardless, I could see a finalised human version of this drug as being very volatile in terms of possible misuse. Although obesity afflicts more individuals than ever, it is still important to differentiate between a naturally heavy physique and true obesity. It is well documented that physical well-being can be more effectively structured through proper diet and regular excercise as opposed to directly losing weight (flaws in the BMI system demonstrate this). On the inside, a heavy-set person might actually be a lot healthier than someone who appears fit on the outside. It's all about the operation of the organs ultimately. An interesting find all the same however. Used correctly, this drug could have the potential for a lot of good. Obviously side effects would have to be monitored very closely if it's ever going to be used medically.
  6. cra$h
    well, Ray Bradbury (he wrote farenheit 451) was right. sociaty is doomed to run off artificial everything, and pills are one of the big ones. I'm totally against sociaty being able to cut corners just because they're fucking lazy. A pill this "good" has to have some nasty long-term health effects, since it seems everything else that was considered a miricle drug has its limitations. Pills like this only boost the power of the pharmacuticle companies, and in the near future I predict it's going to surpass anything the oil industries have ever seen. This is the future, and it's looking real bad.
  7. ShawnD
    Awesome!


    http://en.wikipedia.org/wiki/Caffeine

    Damn. So much research, and in the end it's not even better than caffeine.
  8. Purest
    Dinosaur likes the sound of this drug, although for people such as himself who tend to slip in and out of eating disorders its abuse potential is huge, he would happily offer himself as a test subject however, being paid to lose weight doing nothing, sounds like heaven.
  9. Politicalchalk
    Yea, this definitely reeks of preludes to dystopia where we'll either live in a great big sky-city feasting on chemical buffets, or live below in the savage lands scraping up what meat falls from the sky...
  10. Nature Boy
    That's what I was thinking. I mean, isn't this proposed drug just another stimulant with all their negative side effects? I think this is slightly sensationalised journalism from someone who doesn't have a good understanding of drugs, drug history and their potential uses.
  11. Samadhi
    He invented amphetamines... oh wait
    :crazy

    if this is real, then the world as we know it is in an even more dire hell-spin that it already is. What a waste of time on these scientists part, shame on them. Instead of devoting time to help the world or do viable research, they decided to make this, another way America can get out of doing to work. This one is going to replace the late-night comody central commercials for Lipozene... grr

    :mad:
  12. leadcoffin
    Sorry for posting a misleading title. Another aspect of their research is application in bedridden and otherwise atrophied patients.
  13. cra$h
    but the potential for us walkers to abuse is HUGE.
  14. leadcoffin
    This article doesn't delve into the side effects such a drug would have, either. Professional athletes can't use it because of doping regulations. If using substances to improve your daily life is "wrong", then sure. Probably better for those people not to be obese.
  15. Beeker
    Who needs a liver or kidneys anyway? :)
  16. ShawnD
    That's a great application for stimulant drugs, but has this drug shown to be more effective than the cheap (not-patented) plant extracts already on the market, such as ephedrine?

    This raises an interesting question. We already have lots of addictive stimulants like meth, cocaine, and caffeine. We also have nonaddictive stimulants like ephedrine and pseudoephedrine. Where does this new drug fit in, and why is it better than the existing drugs?

    It looks like this is another case where a guy tries to reinvent the wheel just so he can get a patent. Things like cocaine and caffeine cannot be patented because they are extracted from plants, and meth can't be patented because it's over 100 years old.
  17. leadcoffin
    This article does not refer to the drug as being a stimulant. It mimics the effects of aerobic exercise.
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