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Drug Extends Life of Obese Mice


For most people who are morbidly overweight, the surest route to longevity would be to shed their excess kilograms. But it might one day be possible for obese individuals to enjoy longer, more healthful lives without the often difficult weight loss. The authors of a new study report that a drug they've developed substantially increased the lifespan of obese mice.

In laboratory experiments, researchers injected their drug, called SRT-1720, into specially-bred mice. The drug increased the lifespan of middle-aged, obese rodents by 44 percent compared to obese mice not given the drug compound. All the rodents were fed a high fat, sugary diet similar to a western diet.

The research was carried out by a team of scientists led by gerontologist Rafael de Cabo of the National Institute on Aging.

De Cabo says SRT 1720 reduced the risks associated with obesity-related diabetes:

“When we tested the compound at two different doses in mice on a high fat diet, we observed that this compound had tremendous beneficial effects at the level of prevention of the damage induced by the high fat diet in the liver and also in the pancreas and delayed both the onset of disease and improved the longevity of mice that were receiving this compound," said de Cabo.

Obese mice on the lower dose of SRT 1720 lived four percent longer than untreated obese mice. However, none of the treated obese mice lived as long as normal-weight mice that were used for comparison in the experiments.

De Cabo says SRT-1720 activates a protein called SRT 1, which is a member of a family of enzymes within living cells called sirtuins. These enzymes play a central role in metabolism, the chemical processes necessary for producing energy and maintaining life.

The beneficial effect of sirtuins varies from one individual to the next, probably for genetic reasons, the reasearchers say. That may help explain why some people live longer than others. In the case of obese mice, de Cabo says SRT 1720 appears to be safe and effective in promoting longevity.

“It makes them much, much healthier," he said. "So the animals were living a much healthier life. They have plenty of functions so they did not develop some of the impairments that are associated with age.”

Several other experiments are underway to test drugs similar to SRT-1720 - so far, with varied results. In some studies, SRT-1720 and similar drugs did not switch on sirtuins or produce the beneficial effect seen in de Cabo’s study.

The drug in the latest experiments is manufactured by the pharmaceutical company Sirtris, which is now planning human trials of SRT-1720 and more powerful compounds. According to de Cabo, a longevity drug could be available once Sirtris scales the federal government's regulatory hurdles.

“I am assuming that we should be able to see something in five years maybe," said de Cabo. "It takes a long time from the original observation until al molecule can be put all the way through the clinical trials.”

A study on the drug SRT-1720's beneficial effects in obese mice is published in the journal Scientific Reports.

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