Kannan Senthil, Dawany Noor, Kurupati Raj, Showe Louise C, Ertl Hildegund C J
Gene Therapy and Vaccines Program, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
The Wistar Institute Vaccine Center, Philadelphia, Pennsylvania, USA.
Oncotarget. 2016 Mar 22;7(12):13340-53. doi: 10.18632/oncotarget.7958.
We analyzed age-related defects in B cell populations from young and aged mice. Microarray analysis of bone marrow resident antibody secreting cells (ASCs) showed significant changes upon aging, affecting multiple genes, pathways and functions including those that play a role in immune regulation, humoral immune responses, chromatin structure and assembly, cell metabolism and the endoplasmic reticulum (ER) stress response. Further analysis showed upon aging defects in energy production through glucose catabolism with reduced oxidative phosphorylation. In addition aged B cells had increased levels of reactive oxygen-species (ROS), which was linked to enhanced expression of the co-inhibitor programmed cell death (PD)-1.
我们分析了年轻和老年小鼠B细胞群体中与年龄相关的缺陷。对骨髓驻留抗体分泌细胞(ASC)进行的微阵列分析显示,衰老过程中发生了显著变化,影响了多个基因、通路和功能,包括那些在免疫调节、体液免疫反应、染色质结构和组装、细胞代谢以及内质网(ER)应激反应中发挥作用的基因、通路和功能。进一步分析表明,衰老过程中通过葡萄糖分解代谢产生能量存在缺陷,氧化磷酸化减少。此外,老年B细胞中活性氧(ROS)水平升高,这与共抑制因子程序性细胞死亡(PD)-1的表达增强有关。