title: Age-dependent increases in apoptosis/necrosis ratios in human lymphocytes exposed to oxidative stress.
abstract: Unlike apoptosis, mechanisms leading to necrosis are less well understood. Moreover, changes in necrosis as a function of age have not been studied in human lymphocytes. H(2)O(2)-induced death of peripheral lymphocytes (56 healthy donors, 24-95 years) was evaluated by flow cytometry and propidium iodide staining, caspase activation, DNA laddering, and electron microscopy. H(2)O(2)-induced stress was associated with high levels of necrosis in young individuals (≤30 years), whereas progressively enhanced apoptotic death was observed in older donors, without changes in overall lymphocyte survival. Thus, apoptosis/necrosis ratios were inverted in young versus elderly (≥65 years) donors. Death was not accompanied by increased caspase activity and, accordingly, unaffected by caspase inhibition; however, it was almost completely prevented by poly ADP ribose polymerase inhibition. In summary, aging was associated with changes in the apoptosis/necrosis ratios, rather than susceptibility per se to H(2)O(2)-induced death, which was caspase independent but poly ADP ribose polymerase dependent. Understanding this switch in death modes may aid in understanding age-related disorders.
authors.affiliation: Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Independencia, CP. mbehrens@redclinicauchile.cl
authors.forename: Maria I
authors.initials: MI
authors.lastname: Behrens
authors.forename: Monica
authors.initials: M
authors.lastname: Silva
authors.forename: Astrid
authors.initials: A
authors.lastname: Schmied
authors.forename: Felipe
authors.initials: F
authors.lastname: Salech
authors.forename: Hachi
authors.initials: H
authors.lastname: Manzur
authors.forename: Rolando
authors.initials: R
authors.lastname: Rebolledo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bull
authors.forename: Vicente
authors.initials: V
authors.lastname: Torres
authors.forename: Mauricio
authors.initials: M
authors.lastname: Henriquez
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D012016:Reference Values; D055815:Young Adult
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide