Reduced mortality and moderate alcohol consumption: the phospholipase D-mTOR connection.

Many studies have suggested that moderate alcohol consumption reduces mortality. There is also substantial evidence that lifespan is extended with suppression of TOR (target of rapamycin). It was reported recently that rapamycin is able to extend the lifespan of a mammal--implicating the mammalian TOR (mTOR). mTOR has a requirement for the lipid second messenger phosphatidic acid (PA), which is generated by phospholipase D (PLD). Therefore, in principle, suppression of PLD would be similar to treatment with rapamycin. Significantly, PLD utilizes ethanol preferentially over water in the hydrolysis reaction that ordinarily generates PA. In the presence of ethanol, phosphatidyl-ethanol is generated at the expense of PA leading to the suppression of mTOR. This reaction, known as the transphosphatidylation reaction, provides a mechanistic basis for the reduced mortality observed with moderate consumption of alcohol--that being the suppression of mTOR.