Longevity Protein Discovered

A protein that can extend the lifetimes of worms could have implications for human longevity and development of cancers, a new study suggests.

Roundworms (C. elegans) born without the protien called arrestin lived a third longer than normal, while worms with triple the amount of the protein cut their lives short by one-third.

The findings could have implications for humans, because most proteins in worms have human counterparts, according to study researcher Jeffrey L. Benovic, professor and chair of the Department of Biochemistry and Molecular Biology at Thomas Jefferson University. For instance, the human version of one of these longevity proteins is PTEN, a well-known tumor suppressor.

"The links we have found in worms suggest the same kind of interactions occur in mammals although human biology is certainly more complicated," Benovic said. "We have much work to do to sort out these pathways, but that is our goal."

The roundworm is a useful model for studying human diseases and other aspects of human biology, because the worm is much simpler than humans but also has similarities to us. The worm, for example, has one arrestin gene, whereas humans have four. Worms only have 302 neurons compared with the 100 billion or so neurons in the human brain. In addition, their short lifespans of two to three weeks allows for timely observation of effects on longevity.

Taking advantage of this simplicity, Benovic and Aimee Palmitessa, a postdoctoral research fellow at the university, deleted the single arrestin gene in worms to see what would happen. To Palmitessa's surprise, these worms lived significantly longer. She also found that over-expressing arrestin in worms shortened their lifespan.

"A little less arrestin is good – at least for worms," Benovic said.

This isn't the first discovery made regarding longevity in worms. Past research has shown that activity of the insulin-like growth factor-1 (IGF-1) receptor can influence longevity in worms. This same link has been found in fruit flies, mice and humans. Like arrestin, a little less IGF-1 receptor activity is good, Benovic said.

In this study, Benovic and colleagues found that in the worms, arrestin interacted with two other proteins that play a critical role in its ability to regulate longevity. One of those proteins is the tumor suppressor PTEN; mutations in PTEN are involved in a number of different cancers.

Even so, the connection between human arrestin and PTEN is not clear.

"We don't know at this point if human arrestins regulate PTEN function or if anything happens to arrestin levels during the development of cancer," Benovic said. "Do increasing levels turn off more PTEN, thus promoting cancer, or do levels decrease and allow PTEN to be more active?

"If it turns out to be the first scenario – that increasing amounts of arrestin turn off the tumor suppressor activity of PTEN, then it may be possible to selectively inhibit that process," he added.

The study, which will be published in the online edition of the Journal of Biological Chemistry, was funded in part by the National Institutes of Health.

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