Auxiliary Rustproofing: Pumping up damage fighter lengthens fly life-span (Oxidative damage)
Authors: Davenport R. John 
Published: August 2003

Extra doses of a protein-repairing enzyme might help flies live and stay active longer, according to a new study. The results support a popular theory of aging, although some researchers caution that the increase in longevity could be due to hybrid vigor: the vitality that's often shown by crossbred creatures.

As an organism ages, compounds called reactive oxygen species vandalize proteins, DNA, and other molecules and can disrupt their function. Accumulation of damage from such assaults likely contributes to aging (see
"The Two Faces of Oxygen"
). Previous studies hinted that the enzyme methionine sulfoxide reductase A (MSRA)--which reverses oxidation of the amino acid methionine in marred proteins--might be linked to longevity. Mice that lack MSRA don't live as long as normal mice do, and they're especially sensitive to oxidizing chemicals (see
"Gumming Up the Works"
). But the mutation might weaken the mice rather than accelerate aging. No one had tested whether augmenting the amount of MSRA would increase life-span.

To create fruit flies that produce extra MSRA, Ruan and colleagues mated two unrelated inbred fly strains: One harbors an extra copy of the
msrA
gene fused to a stretch of DNA that can activate adjacent genes, and the second carries a gene that encodes a protein capable of binding to the activation sequence and turning on
msrA.
As expected, the progeny churned out liberal amounts of MSRA. The altered flies lived about 70% longer than their parents, which produce normal amounts of the protein. The flies began dying at older ages than the parental controls did, but once they started, the mortality rate was the same. These results suggest that flies with extra MSRA undergo the same aging process as normal flies do, but that the decline begins later.

Further experiments revealed that the long-lived insects resist oxidative damage. Only 10% of flies that manufacture extra MSRA succumbed to the oxidizing chemical paraquat, whereas 60% to 70% of their parents perished from this treatment. The modified flies also retained their reproductive capacity longer than controls did. In addition, a higher percentage of old insects with supplemental MSRA climbed the walls of a test tube than did control flies of the same age. The findings suggest that the enduring creatures enjoy greater vigor in addition to a longer life-span.

Some scientists question whether the protein boost gives the insects extra time. Like plants and humans, flies are more robust when their parents are unrelated to each other. When mothers and fathers are inbred--as they are in the new work--offspring almost always live longer than their progenitors do. Because the current study doesn't account for that phenomenon, the life extension could result from genetic factors other than increased production of MSRA. But if the protein does keep the flies buzzing, the work would support the proposed link between longer life-span and increased resistance to oxidative damage. Furthermore, it would hint that chemical affronts to methionine promote aging.

--R. John Davenport

H. Ruan, X. D. Tang, M.-L. Chen, M. A. Joiner, G. Sun, N. Brot, H. Weissbach, S. H. Heinemann, L. Iverson, C.-F. Wu, T. Hoshi, High-quality life extension by the enzyme peptide methionine sulfoxide reductase.
Proc. Natl. Acad. Sci. U.S.A.,
26 February 2002 [e-pub ahead of print].
[Abstract]
[Full Text]