title: Senescence-induced increases in intracellular oxidative stress and enhancement of the need for ascorbic acid in human fibroblasts.
abstract: Many studies have suggested that there is a close correlation among declines in internal ascorbic acid (AsA) levels, various disorders, and senescence. To clarify the relationships between age-associated changes in intracellular AsA levels and the effects of AsA administration on intracellular reactive oxygen species (ROS) levels, we investigated aging-related changes in AsA uptake, ROS levels, and the effects of AsA administration on intracellular ROS levels in young and old (senescent) human fibroblasts. Our results demonstrated that AsA uptake was increased in old cells compared with young cells, although mRNA and protein expression of sodium-dependent vitamin C transporter 2 was barely altered between the young and old cells. We also demonstrated that the intracellular superoxide anion level was higher in young cells, whereas the level of intracellular peroxides was significantly increased in old cells under both normal and oxidative stress conditions. Moreover, AsA administration markedly decreased the augmentation of intracellular peroxides in old cells, whereas there was no effect of AsA treatment in young cells under both normal and oxidative stress conditions. Therefore, our results also indicate that AsA could play an important role in regulating the intracellular ROS levels in senescent cells and that the need for AsA is enhanced by cellular senescence.
authors.affiliation: Laboratory of Bioscience & Biotechnology for cell function control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara, Hiroshima 727-0023, Japan. ysaito@pu-hiroshima.ac.jp
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Aiko
authors.initials: A
authors.lastname: Morishita
authors.forename: Satomi
authors.initials: S
authors.lastname: Mito
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Tsujiya
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D018384:Oxidative Stress; D010545:Peroxides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060347:Sodium-Coupled Vitamin C Transporters / Q000191:economics* / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D010545:Peroxides; D017382:Reactive Oxygen Species; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D013481:Superoxides; D001205:Ascorbic Acid