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Drugs could turn couch potatoes into athletes

Drugs could turn couch potatoes into athletes

作者:侴杂蟪  时间:2019-03-01 09:17:13  人气:

By Ewen Callaway People too busy – or lazy – to go for a run or hit the gym could swallow a pill and get the same boost, thanks to two different drugs that make mice run longer and further than un-doped mice. “The first group that will use [them] is athletes,” says Ronald Evans, a molecular biologist at the Salk Institute in La Jolla, California. “Athletes have a very low threshold for experimenting with and using performance-enhancing drugs, and I have no doubt they will be the early adopters of both drugs.” The drugs seem to work by activating a key metabolic protein called PPAR-delta, which tells cells to burn extra fat and make more mitochondria – the cell’s power-producing structures. In 2004, Evans’ team showed that “marathon mice”, genetically engineered to crank up the protein, outpace normal mice on a treadmill. Evans and his colleague Vihang Narkar wanted to see whether a drug that activates PPAR-delta could turn regular adult rodents to miniature marathon winners. But the drug – called WG1516 – did nothing for the mice but switch on a handful of genes in their muscles. However, when the researchers paired doses of WG1516 with a month of training – half an hour on a treadmill, five days a week – mice given the drug jogged longer and further than drug-free mice. They averaged three kilometres over three-and-a-half hours compared with 1.8 kilometres and about two hours for normal mice. Their muscles boasted more of the “slow-twitch” fibres important for endurance. The drug combined with exercise also revved up their mitochondria to produce more energy and turned on a larger group of “exercise” genes, than the chemical alone. The drug’s failure in sedentary mice surprised Evans, but he suspects that activating PPAR-delta in adults requires the added jolt of exercise. “The way that you or I would remodel our muscles is through exercise. If you lift weights you’re going to get stronger.” Next, Evans and Narkar wondered whether PPAR-delta’s effects might be connected to another protein shown to boost muscle growth. This protein, called AMPK, senses when cells are running out of fuel and makes more. The researchers tested a drug called AICAR, which tricks AMPK into never shutting off production. Mice that took AICAR for a month could run about 44% longer than untreated mice, even without prior training. “This is the couch potato experiment,” Evans says. This drug also “turned up” many of the same muscle genes as WG1516, when combined with exercise, suggesting that AMPK triggers PPAR-delta during exercise, Evans says. However, Lee Witters, a biochemist at Dartmouth University in Hanover, New Hampshire, US, notes that AICAR has other effects on energy balance, and revving up AMPK might not be the only reason that mice run longer. But would-be dopers probably won’t wait for biochemical certainty or safety tests to dabble. “I’m sure if word gets to Beijing quickly, there may be some people popping AICAR,” he says. It and WG1516 are already available to determined dopers. A 2003 journal article details a recipe for WG1516; while a biochemical supply company sells a mouse’s three-month supply of AICAR for 350 euros. Humans, however, would need far more of the drug to see any benefit. Elite athletes looking for even the slightest upper hand should beware, though – Evans’s team developed a simple test for both drugs that may be ready in time for next week’s Olympics in Beijing. In any case, blood and urine samples can be tested for the drugs after the Olympics, he says. Rather, Evans hopes the drugs – or related compounds – might someday treat obesity. “It’s possible to make a pill – an exercise pill – that can actively improve physical performance and endurance without ever having exercised,” he says. Journal reference: Cell (DOI: