Replicative senescence induced by Romo1-derived reactive oxygen species.
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.
Chung
Young Min
YM
Graduate School of Medicine and Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 136-705.
Lee
Seung Baek
SB
Kim
Hyung Jung
HJ
Park
Seon Ho
SH
Kim
Jung Jin
JJ
Chung
Jin Sil
JS
Yoo
Young Do
YD
D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*
D045222:Electron Transport Chain Complex Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species