Enzyme May Play Key Role in Aging

Lower levels of substance result in longer life, study finds

Nov. 29 &emdash; Scientists are a step closer to understanding why eating less leads to longer life. In a report in Friday’s edition of the journal Science, researchers said studies with fruit flies, which have many genes similar to mammals, showed that an enzyme called Rpd3 histone deacetylase likely is a key to longevity.

In the study, flies with genetic mutations that resulted in lower levels of the enzyme lived about 33 percent or 50 percent longer than normal.

Studies in yeast, rodents and other organisms have found that drastically cutting calories extends life span, and researchers are striving to find out how that happens. The hope is that human drugs may be developed to mimic that effect, without having to eat less.

The enzyme Rpd3 histone deacetylase may shed light on the process. "If you decrease the level of enzyme without eating less, you still get life span extension," said Stewart Frankel, a Yale research scientist and the study’s senior author.

In the study, flies with genetic mutations that resulted in lower levels of the enzyme lived about 33 percent or 50 percent longer than normal. With a low-calorie diet, life span was extended by about 41 percent.

The enzyme may be an attractive drug target, said Frankel. Frankel cautioned that much more research, which probably will take several years, is needed before scientists find a drug that can safely provide the same effect in people. The drug would have to be convenient and safe to take for many years, he said. 
 
One drug, called phenylbutyrate, is thought to target the Rpd3 enzyme, Frankel said. A study published earlier this year showed that feeding that drug to fruit flies extended their lives. Low-calorie diets produce other benefits aside from longer lives, according to past studies in rodents that evaluated the effect of decreasing caloric intake by 20 to 40 percent. "Their memory is better, their muscle tone is better, they get fewer cancers, fewer heart problems," Frankel said. Even gray hair is delayed.

The study was co-authored by Blanka Rogina and Stephen Helfand of the University of Connecticut Health Center.