The contribution of oxidative stress to platelet senescence during storage

BACKGROUND: Platelets for transfusion become senescent and dysfunctional during storage, resulting in a markedly short shelf life (5 days). We hypothesized that oxidative stress might account for this decline. STUDY DESIGN AND METHODS: Human platelets were treated with or without antioxidants before storage, and samples were collected and analyzed at different time points. Platelet senescence was determined by senescence-associated beta-galactosidase assay, and senescence-related platelet qualities were also analyzed. RESULTS: Sign of senescence became evident after Day 3 and continued to increase over time. We also found that chemical induction of platelet activation did not affect senescence level, whereas apoptosis inducers showed a stimulative effect on platelet senescence. Moreover, this effect was not prevented by a pancaspase inhibitor. Meanwhile, cellular and mitochondrial reactive oxygen species were found elevated during storage, and treatments with antioxidants successfully prevented this increase and also mitigated senescence levels of stored platelets. Finally, resveratrol, a natural antioxidant, was utilized as a novel storage additive to safely extend platelet shelf time. We showed that the addition of resveratrol efficiently postponed platelet senescence and ameliorated platelet storage lesion. CONCLUSIONS: Platelets during storage became senescent and dysfunctional over time, and we found that oxidative stress might account for this decline. The addition of antioxidants effectively postponed senescence and ameliorated platelet storage lesion, which might provide a valuable reference to future platelet storage methodologies.