November 04, 2008

Resveratrol Follow Up Drug 1000 Times More Potent

A new drug proves effective in fighting obesity and related diseases while increasing stamina in mice and mimics calorie-restricted diet.

Estimates of life extension from calorie restriction are 3 to 13 years.

The effects of the compound are similar to those of resveratrol, a molecule found in red wine that has previously been shown to extend life span and have health benefits in mice. But SRT1720 is a thousand times more potent than resveratrol, meaning that it could be taken in smaller doses. A person would have to drink hundreds of glasses of wine to get the same health benefits from resveratrol, and, while supplements are available, it is unclear whether they are as effective. "Resveratrol will pretty soon look like ancient technology," says Sinclair.

It is significant that the drug mimics the effects of a calorie-restricted diet, since this has previously been tied to increased life expectancy, says William Evans, a professor of geriatric medicine, nutrition, and physiology at the University of Arkansas for Medical Sciences.

It's as if the couch-potato mice underwent a strict diet and exercise regime, says David Sinclair, a biologist at Harvard Medical School, in Boston, who is one of the cofounders of Sirtris but was not involved in the current study. The new study "is a major step forward, showing that we can design and synthesize potent, druglike molecules that could slow down the aging process," says Sinclair.

Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009. "We could know as early as next year if the same types of benefits we see in mice, we see in humans," he says.

The potential longevity-enhancing drug has passed its final animal testing challenge, pushing closer to reality the dream of all-purpose drugs against diseases of aging.

Mice given the new drug, called SRT1720, gorged on high-fat food for four months without gaining weight or developing diabetes, and ran twice as far on a treadmill as their control-group counterparts. Similar drugs are expected to follow down the pipeline.

Curing the buildup of junk in the lysosome has the potential to extend human life more, perhaps 20-40 years.

Cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures that are so weird that none of the cell's degradation machinery works on them.

This situation is very rare, but in the long run these modified chemicals add up. Ultimately the chemicals end up in the lysosome, a special vessel that contains the most powerful degradation machinery in the cell; if something can't be broken down there, it just stays there forever. This doesn't matter in cells that divide regularly, because division dilutes the junk enough that it remains at harmlessly low levels, but non-dividing cells gradually fill up with this stuff, making them dysfunctional. The heart, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery wall all suffer from this.

Eventually, these cells can't process any more of this junk, and they stop working correctly. This failure is the key cause of atherosclerosis (the unstable buildups, called plaques, that build up in the artery wall and eventually burst and cause heart attacks and strokes).

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