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Drug related to resveratrol showing promise in extending lifespan of the obese

Dominika Osmolska Psy.D.'s picture

The human race has been on a quest for the fountain of youth for as long as it has been able to reflect on its own mortality. Researchers from many fields continue to pursue the holy grail of longevity, including geneticists, biochemists and nanotechnologists. Now researchers who have synthesized a compound originally discovered in red wine say they are on to something.

The drug, SRT-1720, appears to substantially extend the average life span of mice, even ones which are obese. In fact, it seems to protect obese mice by reducing the amount of fat in the liver and increasing sensitivity to insulin, despite the mice love handles. These and other positive health effects enable the obese mice to live 44 percent longer, on average, than obese mice that did not receive the drug, according to a team of researchers led by Rafael de Cabo, a gerontologist at the National Institute on Aging.

The findings “demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals,” Dr. de Cabo and colleagues write in Thursday’s issue of the new journal Scientific Reports.

The scientists stress that they are not looking for a drug which will enable us to live an over-indulgent lifestyle free of consequences, but rather, they are looking for a substance which will stave off the degenerative effects of normal aging. The idea is to come up with a compound which mimics the effects of a very low-calorie diet – which has been demonstrated to extend health and longevity significantly – without the brutal regimen of such an eating plan. Remember that in previous animal trials, obese, diabetic mice lifespans were extended 30 percent by the consumption of resveratrol – but that extension simply caught up to the normal, non-obese mice lifespan. In other words, resveratrol might curtail an early death for those who abuse their health, not give them extra or even particularly healthy, years.

“The drugs could be used as a preventative to stave off diseases, but I don’t think they will ever be an excuse to abuse your body,” said David Sinclair, a biologist at Harvard Medical School and co-chairman of the scientific advisory board of Sirtris, which developed SRT-1720.

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The company, a small pharmaceutical concern in Cambridge, Mass., designed SRT-1720 and a set of similar drugs to mimic resveratrol — the trace ingredient of red wine that is thought to activate protective proteins called sirtuins.

It is the sirtuins which help mice and other mammals live longer when they are placed on a restricted calorie diet. Something about profound calorie reduction helps release sirtuins, but most people cannot stick to such a Spartan diet. Resveratrol offered the hope of a less painful path than calorie restriction which led to the same effects.

Unfortunately, large doses of resveratrol are required to show any effect, so chemical mimics like SRT-1720 were developed to activate sirtuin at much lower doses (sorry, red wine, but at one milligram of resveratrol per glass, you are not quite the elixir of youth we had hoped you would be).

Despite the positive new results with SRT-1720, Sirtris is not putting it into clinical trials because the company believes another of its resveratrol mimics, SRT-2104, is more promising. That drug “is more suitable for human consumption,” said Dr. Sinclair, a co-author of Dr. de Cabo’s report. “Questions were raised about the molecules and if they are working the way we said they were,” Dr. Sinclair said. “But with this paper, the weight of evidence is shifting back in favor of the premise that we can tweak the aging pathway with drugs.”

Dr. de Cabo and his team included normal, untreated lean mice in their study as a control group for the treated and untreated fat mice. The treated fat mice lived longer than the untreated ones, but died long before the normal mice. Although the treated fat mice lived significantly longer on average, there was little difference between their maximum life span and that of the untreated mice. The drug, in other words, helped the fat mice enjoy more of their available life span without increasing the span itself.

The research would be even more exciting if scientists could demonstrate that they can extend the life span of normal, lean mice. Although healthy, lean mice were also part of the study, the results on that population are still pending because, according to de Cabo, the lean mice were taking a lot longer to die. Those results will be published early next year.