Tang Z, Zhang Z, Zheng Y, Corbley M J, Tong T
Department of Biochemistry, Beijing Medical University, China.
Mech Ageing Dev. 1994 Jan;73(1):57-67. doi: 10.1016/0047-6374(94)90038-8.
The limited replicative life span of diploid human cells in vitro (cellular senescence) serves as a cellular model of aging. We examined the proliferative response of 2BS cells of different population doubling levels to epidermal growth factor (EGF). DNA synthesis was measured by thymidine incorporation. As the cells aged, there was a significant decrease both in the baseline level of DNA synthesis and in the stimulation of DNA synthesis by EGF addition. The effective concentration of EGF and the latent period prior to DNA synthesis did not change. EGF receptor mRNA expression also remained unchanged as the cells aged, in the absence or presence of EGF, suggesting that the defect in old cells lies downstream in the EGF signaling pathway. As the cells reached 100% of their life span, however, there was a 70% decrease in EGF receptor mRNA. Expression of the EGF receptor homologue HER-2 was also examined. The HER-2 mRNA level was significantly reduced in old cells. Moreover, HER-2 expression was stimulated by EGF addition in young cells but not in old cells. The results suggest that cell aging is associated with a progressive loss in the ability of cells to respond to growth factors.
二倍体人类细胞在体外的有限复制寿命（细胞衰老）可作为衰老的细胞模型。我们检测了不同群体倍增水平的2BS细胞对表皮生长因子（EGF）的增殖反应。通过胸腺嘧啶核苷掺入法测定DNA合成。随着细胞衰老，DNA合成的基线水平以及添加EGF后对DNA合成的刺激均显著降低。EGF的有效浓度以及DNA合成前的潜伏期未发生变化。无论有无EGF，随着细胞衰老，EGF受体mRNA表达也保持不变，这表明衰老细胞中的缺陷位于EGF信号通路的下游。然而，当细胞达到其寿命的100%时，EGF受体mRNA下降了70%。我们还检测了EGF受体同源物HER-2的表达。老年细胞中HER-2 mRNA水平显著降低。此外，添加EGF可刺激年轻细胞中HER-2的表达，但对老年细胞无此作用。结果表明，细胞衰老与细胞对生长因子反应能力的逐渐丧失有关。
