Secretory phospholipase A(2) (sPLA(2)) is involved in various cellular physiological and pathological responses, especially in inflammatory responses. Accumulating evidence suggests that inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. However, the involvement of sPLA(2) in cellular senescence is not clear. In this study, we found that sPLA(2) treatment induces cellular senescence in human dermal fibroblasts (HDFs), as confirmed by increases in senescence-associated beta-galactosidase activity, changes in cell morphology, and upregulation of p53/p21 protein levels. sPLA(2)-induced senescence was observed in p16-knockdown HDFs and p16-null mouse fibroblasts, but not in p53-knockdown HDFs and p53-null mouse fibroblasts. Treatment with sPLA(2) increases reactive oxygen species (ROS) production, and an antioxidant, N-acetylcysteine, inhibits sPLA(2)-induced cellular senescence. These results suggest that sPLA(2) has a role in cellular senescence in HDFs during inflammatory response by promoting ROS-dependent p53 activation and might therefore contribute to inflammatory disorders associated with aging.

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An innovative nuclear fuel concept for the utilization as energy resources and for the incineration of excess Pu arisings as well as for an effective transmutation of minor actinides (MA's; Am, Np and Cm) is discussed from the aspect of material technology. Stabilized cubic phase ZrO 2 and other potential candidate materials for the Inert Matrix are compared in terms of the material properties and other behaviors such as the behavior against irradiation with the relevant information currently available. Strategies for the use of the Inert Matrix Fuel concept in various countries are discussed and compared for their options in nuclear fuel cycle technology.

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