Age-Dependent Increases in Apoptosis/Necrosis Ratios in Human Lymphocytes Exposed to Oxidative Stress

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. H2O2-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. H2O2-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 H2O2-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.