Sci. Aging Knowl. Environ., 28 November 2001
Vol. 2001, Issue 9, p. nw30
[DOI: 10.1126/sageke.2001.9.nw30]


Running Low But Long: Mutation in energy production machinery extends life in worms (Oxidative stress)

Mary Beckman;2001/9/nw30

Key Words: oxidative stress • isp-1 • reactive oxygen species • life-span • worm

Abstract: Some people think stress kills--and the image of the businessman nearly popping his jugular isn't all they're thinking about. Researchers have long pursued the connection between oxidative stress and aging. While generating the adenosine triphosphate that powers the cell, mitochondria also give birth to the byproduct superoxide, a highly reactive oxygen radical that can damage other molecules. To protect the cell, resident enzymes turn superoxide into the slightly less obnoxious peroxide and then into innocuous water--but they don't neutralize it all. Some researchers propose that the havoc wreaked by these reactive oxygen species (ROS) promotes aging (see "The Two Faces of Oxygen"), based in part on observations that an antioxidant drug and mutations that disrupt global energy-producing activities can extend worm and yeast life-spans, respectively. Although no one has clearly shown that ROS shorten life, circumstantial evidence is mounting. Now, researchers add another piece of data to the pile: A mutation in a gene that normally promotes ROS production lengthens life-span in worms.

In their search for a connection between oxidative damage and aging, Hekimi and colleagues generated a collection of Caenorhabditis elegans strains that carried random mutations and identified some with extended life-spans. Further analysis revealed that one of them carries an alteration in the gene that encodes the iron sulfur protein (ISP-1). ISP-1 is a go-between for two proteins in the mitochondrial energy generator as well as a culprit in ROS production: ISP-1 passes electrons from cytochrome b to cytochrome c and can create superoxide in the process. Worms that harbor the mutation in isp-1 live up to twice as long as normal, and their physiology differs in other ways as well. They lay fewer eggs, defecate more slowly--and consume about half the oxygen as do wild-type animals. The latter result suggests to the researchers that the mutant worms make fewer ROS; however, the team didn't directly measure ROS production, and other phenomena could also explain the findings.

More work is necessary to nail down exactly how changes in isp-1 lead to its newly discovered life-extending power, but the new addition to the collection of genes that affect oxidative damage and aging might help scientists understand how these phenomena are connected.

--Mary Beckman; suggested by Matt Kaeberlein

J. Feng, F. Bussiļæ½re, S. Hekimi, Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev. Cell 1, 633-644 (2001). [Abstract] [Full Text]

Citation: M. Beckman, Running Low But Long: Mutation in energy production machinery extends life in worms (Oxidative stress). Science's SAGE KE (28 November 2001),;2001/9/nw30

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