title: Iron accumulation during cellular senescence.
abstract: Iron accumulates as a function of age and is associated with the pathology of numerous age-related diseases. These changes may be caused by altered iron homeostasis at the cellular level, yet this is poorly understood. Therefore, changes in iron content in primary human fibroblasts were studied in culture models of cellular senescence. Total iron content increased exponentially during cellular senescence, reaching approximately 10-fold higher levels than young cells. Increasing intracellular iron levels through iron-citrate supplementation or decreasing intracellular iron levels using iron-selective chelators had little effect on cellular life span and markers of cellular senescence when used at subtoxic doses. However, accelerating cellular senescence with low-dose H(2)O(2) also accelerated senescence-associated iron accumulation. Delaying cellular senescence with N-tert-butyl-hydroxylamine (NtBHA) attenuated senescence-associated iron accumulation. Furthermore, H(2)O(2) or NtBHA had no effect on iron intracellular levels in immortalized fibroblasts. Thus, iron accumulation is not a cause, but a consequence of normal cellular senescence in vitro. Senescence-associated iron accumulation may contribute to the increased oxidative stress and cellular dysfunction seen in senescent cells.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Killilea
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Wong
authors.forename: Hendry S
authors.initials: HS
authors.lastname: Cahaya
authors.forename: Hani
authors.initials: H
authors.lastname: Atamna
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000375:Aging; D000818:Animals; D016922:Cellular Senescence; D002614:Chelating Agents / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006898:Hydroxylamines / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype
chemical_list: D002614:Chelating Agents; D006898:Hydroxylamines; C072771:N-tert-butylhydroxylamine; D006861:Hydrogen Peroxide; D007501:Iron