Pignolo R J, Martin B G, Horton J H, Kalbach A N, Cristofalo V J
Center for Gerontological Research, Allegheny University of Health Sciences, Philadelphia, Pennsylvania 19129, USA.
Exp Gerontol. 1998 Jan-Mar;33(1-2):67-80. doi: 10.1016/s0531-5565(97)00090-9.
Senescent human diploid fibroblasts have an undefined arrest state partially characterized by the differential expression of cell cycle-regulated genes and a failure to complete the mitogen-stimulated cascade of signalling events that lead to DNA synthesis. We present evidence that this arrest state precludes the entry of senescent fibroblasts into a normally reversible G0 or quiescent state. Both nuclear association kinetics and quinacrine dihydrochloride nuclear fluorescence show chromatin condensation patterns consistent with arrest in late G1 and exclusion of senescent cells from the G0 phase of the cell cycle. Steady-state thymidine kinase mRNA levels indicate that some of the signalling cascades initiated from a functional G0 state may be intact in senescent cells, at least qualitatively, and that this expression may represent an abortive attempt to complete pathways required for DNA replication. Taken together, the evidence suggests that growth arrest in senescent cells likely occurs in a physiologic state fundamentally distinct from that of the G0, quiescent state that is achieved by nonproliferating young cells. A full response to serum or growth factor addition, leading from quiescence to DNA synthesis, may require cells to initiate this traverse from a true G0 state. If so, senescent cells would be excluded from this pathway.
衰老的人二倍体成纤维细胞具有一种未明确的停滞状态，其部分特征为细胞周期调控基因的差异表达，以及无法完成有丝分裂原刺激的信号事件级联反应，而这些反应会导致DNA合成。我们提供的证据表明，这种停滞状态使衰老的成纤维细胞无法进入正常可逆的G0期或静止状态。核结合动力学和盐酸喹吖因核荧光均显示出染色质浓缩模式，这与细胞停滞在G1晚期以及衰老细胞被排除在细胞周期的G0期一致。稳态胸苷激酶mRNA水平表明，从功能性G0状态启动的一些信号级联反应在衰老细胞中可能至少在定性上是完整的，并且这种表达可能代表了完成DNA复制所需途径的失败尝试。综合来看，证据表明衰老细胞中的生长停滞可能发生在一种与非增殖年轻细胞所达到的G0静止状态根本不同的生理状态。对血清或生长因子添加的完全反应，即从静止状态到DNA合成，可能需要细胞从真正的G0状态开始这种转变。如果是这样，衰老细胞将被排除在这条途径之外。
