期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 122, 期 11, 页码 1151-1167出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/S0047-6374(01)00254-8
关键词
T cell clone replicative lifespans; oxidative DNA damage; cyclin-dependent kinase inhibitors; p16; p21; p27
T cells in vivo have been shown to accumulate DNA damage with age. To investigate the effects of DNA damage on T cell biology we have utilised an in vitro human CD4+ T cell clone model. Levels and types of DNA damage were determined in 11 independent T cell clones as a function of their in vitro lifespan. Increased levels of reactive oxygen species (ROS) induced DNA damage with increasing age were found in all clones analysed using a modified alkaline comet assay. T cell clones underwent apoptosis at the end of their lifespans. There were no consistent changes in the mRNA levels for the cyclin-dependent kinase inhibitors (CKI) p16, p21, and p27 during the clones' lifespans. It appears that the increased levels of ROS induced DNA damage in the T cells is not the major trigger of apoptosis, via the p53/p21 pathway. In addition, at the end of their lifespans, the T cell clones did not display the CRI phenotype reported for senescent cells tan increase in p16 and p21 levels). Thus, while the T cell clones appear sensitive to ROS-induced DNA damage, the molecular mechanisms through which this influences T cell dysfunction with age remains to be elucidated. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据