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Bile Acids and Yeast Longevity

Earlier this year, researchers screening potential longevity-enhancing compounds in yeast turned up the bile acid lithocholic acid:

the Titorenko laboratory [tested] the hypothesis that networks exist within cells that are not inducible, but act constitutively to extend the lifespan of cells regardless of nutrient availability ... [the study] presents an original screen designed to isolate molecules that further lengthen the life span of yeast under calorie restriction rather than imitating this effect. ... Among the chemical compounds identified, the authors focus on one group representing 6 bile acids compounds, the most efficient of them being lithocholic acid (LCA). Bile acids are mildly toxic oxidized derivatives of cholesterol that play important roles in lipid uptake by the intestine.

That screen was looking for compounds that work on top of calorie restriction - i.e. that must operate through some different and potentially new longevity-enhancing mechanism. It's a clever way of covering more ground in the study of metabolism. Here's a more readable summary from the popular science press:

"Our findings imply that LCA extends longevity by targeting two different mechanisms," says first author Alexander Goldberg, a Concordia doctoral student. "The first takes place regardless of the number of calories and involves the day-to-day or housekeeping proteins. The second system occurs during calorie-restriction and involves stressor proteins."

...

"Although we have an overall idea how LCA works to extend longevity in yeast, we still need to determine if this is the case for other species," says Titorenko. "We do know from previous studies, however, that bile acids are beneficial to health and longevity. For example, they have shown to accumulate in the serum of long living mice and play a role in improving rodent liver and pancreatic function."

On the other hand, you'll also find evidence for LCA to be a toxic cancer risk in mice:

"Lithocholic acid is highly toxic, and it builds up in a high-fat diet," Mangelsdorf said. "We don’t know how it causes cancer; but it is known to cause cancer in mice, and people with colon cancer have high concentrations of it."

So it seems a little early to be doing anything other than noting this as interesting - and in the long term, the value of this research will be to draw more attention to the biological mechanisms by which LCA works to extend life in yeast.

Comments

This I find very interesting research, because it seems that there may be a link between non-alcoholic fatty liver disease and atherosclerosis. This disease reduces the production of bile acids ergo, less cholesterol and calcium breakdown which may cause atherosclerosis. It seems its also linked to gall stones (calcium deposits).
Regarding lithocholic acid and cancer I found this earlier paper of some interest: http://carcin.oxfordjournals.org/content/21/5/999.full
It seems from this research that it may only be cancerous when a carcinogen is present, and it seems to induce apoptosis!

Posted by: Andrew Simpson at September 18th, 2010 1:54 AM

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