Journal of Biological Chemistry
Volume 283, Issue 48, 28 November 2008, Pages 33763-33771
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Molecular Basis of Cell and Developmental Biology
Replicative Senescence Induced by Romo1-derived Reactive Oxygen Species*

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Persistent accumulation of DNA damage induced by reactive oxygen species (ROS) is proposed to be a major contributor toward the aging process. Furthermore, an increase in age-associated ROS is strongly correlated with aging in various species, including humans. Here we showed that the enforced expression of the ROS modulator 1 (Romo1) triggered premature senescence by ROS production, and this also contributed toward induction of DNA damage. Romo1-derived ROS was found to originate in the mitochondrial electron transport chain. Romo1 expression gradually increased in proportion to population doublings of IMR-90 human fibroblasts. An increase in ROS production in these cells with high population doubling was blocked by the Romo1 knockdown using Romo1 small interfering RNA. Romo1 knockdown also inhibited the progression of replicative senescence. Based on these results, we suggest that age-related ROS levels increase, and this contributes to replicative senescence, which is directly associated with Romo1 expression.

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*

This work was supported by Grant FG06-2-20 from the 21st Century Frontier Functional Human Genome Project funded by the Korea Government (MEST), by Grant R01-2006-000-10113-0 from the Basic Research Program of the Korea Science and Engineering Foundation, and by Grant R11-2005-017-01001-0 from the Research Center for Woman's Diseases of the Korea Science and Engineering Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

Both authors contributed equally to this work.