Minuscule amounts of ethanol, the type of
alcohol found in alcoholic beverages, can more than double the life span of a
tiny worm known as Caenorhabditiselegans, which is used
frequently as a model in aging studies, University
of California, Los Angeles (UCLA) biochemists report. The
scientists said they find their discovery difficult to explain.
“This finding floored us—it’s
shocking,” said Steven Clarke, a UCLA professor of chemistry and
biochemistry and the senior author of the study, published online in PLoS ONE.
In humans, alcohol consumption is generally
harmful, Clarke said, and if the worms are given much higher concentrations of
ethanol, they experience harmful neurological effects and die, other research
“We used far lower levels, where it may
be beneficial,” said Clarke, who studies the biochemistry of aging.
The worms, which grow from an egg to an
adult in just a few days, are found throughout the world in soil, where they
eat bacteria. Clarke’s research team—Paola Castro, Shilpi Khare, and Brian
Young—studied thousands of these worms during the first hours of their lives,
while they were still in a larval stage. The worms normally live for about 15
days and can survive with nothing to eat for roughly 10 to 12 days.
“Our finding is that tiny amounts of ethanol
can make them survive 20 to 40 days,” Clarke said.
Initially, Clarke’s laboratory intended to
test the effect of cholesterol on the worms. “Cholesterol is crucial for
humans,” Clarke said. “We need it in our membranes, but it can be
dangerous in our bloodstream.”
The scientists fed the worms cholesterol,
and the worms lived longer, apparently due to the cholesterol. They had
dissolved the cholesterol in ethanol, often used as a solvent, which they
“It’s just a solvent, but it turns out
the solvent was having the longevity effect,” Clarke said. “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
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,” Clarke said.
Why would such little ethanol have such an
effect on longevity?
“We don’t know all the answers,”
Clarke acknowledged. “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.”
The scientists found that when they raised the
ethanol level by a factor of 80, it did not increase the life span of the
The research raises, but does not answer,
the question of whether tiny amounts of ethanol can be helpful for human
health. Whether this mechanism has something in common with findings that
moderate alcohol consumption in humans may have a cardiovascular health benefit
is unknown, but Clarke said the possibilities are intriguing.
In follow-up research, Clarke’s laboratory
is trying to identify the mechanism that extends the worms’ life span.
About half the genes in the worms have human
counterparts, Clarke said, so if the researchers can identify a gene that
extends the life of the worm, that may have implications for human aging.
“It is important for other scientists
to know that such a low concentration of the widely used solvent ethanol can
have such a big effect in C. elegans,”
said lead author Paola Castro. “What is even more interesting is the fact
that the worms are in a stressed developmental stage. 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.”
“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.
“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-mm–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.”