Alcohol is a Fountain of Youth

UCLA biochemists have discovered a fountain of youth in tiny drops of alcohol, for worms at least.

In a recent study, minuscule amounts of ethanol - the type of alcohol found in alcoholic beverages - more than doubled the life span of a tiny worm known as Caenorhabditis elegans.

The scientists are dumbfounded.

"This finding floored us — it's shocking," said UClA biochemistry professor Steven Clarke, senior author of the study published January 18, 2012, in the online journal PLoS ONE, a publication of the Public Library of Science.

As with humans, alcohol consumption
is generally harmful to the worms. Those given higher concentrations of ethanol experience neurological problems and die. But when fed tiny amounts, the results are remarkably beneficial. Worms which normally live for about 15 days survived 20 to 40 days.

"At high magnifications under the microscope, it was amazing to see how the worms given a little ethanol looked significantly more robust than worms not given ethanol," said UCLA bioengineer Paola Castro.

Caenorhabditis elegans is commonly used as a model in aging studies, as half the genes in the worms have human counterparts Found throughout the world in soil, where they eat bacteria, the worm grows from an egg to an adult in just a few days.

Initially, Clarke's team of scientists were testing the effect of cholesterol on the worms.



They fed the worms cholesterol, and the worms lived longer, apparently due to the cholesterol. But they had dissolved the cholesterol in a solvent, ethanol, diluted 1,000-fold. 

"It's just a solvent, but it turns out the solvent was having the longevity effect," Clarke explained. "The cholesterol did nothing. We found that not only does ethanol work at a 1-to-1,000 dilution, it works at a 1-to-20,000 dilution. That tiny bit shouldn't have made any difference, but it turns out it can be so beneficial."

How little ethanol is that?

"The concentrations correspond to a tablespoon of ethanol in a bathtub full of water or the alcohol in one beer diluted into a hundred gallons of water."

Why would such little ethanol have such an effect on longevity?

"We don't know all the answers. It's possible there is a trivial explanation, but I don't think that's the case. We know that if we increase the ethanol concentration, they do not live longer. This extremely low level is the maximum that is beneficial for them."



Could simiarly tiny amounts of ethanol be helpful for human health? After all, recent studies suggest that moderate alcohol consumption has cardiovascular health benefits.

In follow-up research, Clarke's laboratory is trying to identify the mechanism that extends the worms' life span. If the researchers can identify a gene that extends the life of the worm, that may have implications for human aging.

"While the physiological effects of high alcohol consumption have been established to be detrimental in humans, current research shows that low to moderate alcohol consumption, equivalent to one or two glasses of wine or beer a day, results in a reduction in cardiovascular disease and increased longevity," said co-author Shilpi Khare, a former Ph.D. student in UCLA's biochemistry and molecular biology program who is now a postdoctoral fellow at the Genomics Institute of the Novartis Research Foundation in San Diego. "While these benefits are fascinating, our understanding of the underlying biochemistry involved in these processes remains in its infancy.

"We show that very low doses of ethanol can be a worm 'lifesaver' under starvation stress conditions," Khare added. "While the mechanism of action is still not clearly understood, our evidence indicates that these 1 millimeter–long roundworms could be utilizing ethanol directly as a precursor for biosynthesis of high-energy metabolic intermediates or indirectly as a signal to extend life span. These findings could potentially aid researchers in determining how human physiology is altered to induce cardio-protective and other beneficial effects in response to low alcohol consumption."

Clarke's laboratory identified the first protein-repair enzyme in the early 1980s, and his research has shown that repairing proteins is important to cells. In the current study, the biochemists reported that life span is significantly reduced under stress conditions in larval worms that lack this repair enzyme. (More than 150 enzymes are involved in repairing DNA damage, and about a dozen protein-repair enzymes have been identified.)

"Our molecules live for only weeks or months," Clarke said. "If we want to live long lives, we have to outlive our molecules. The way we do that is with enzymes that repair our DNA — and with proteins, a combination of replacement and repair."

sources:

Brian Young, David Geffen School of Medicine at UCLA