Stewart Sheila A, Ben-Porath Ittai, Carey Vincent J, O'Connor Benjamin F, Hahn William C, Weinberg Robert A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Nat Genet. 2003 Apr;33(4):492-6. doi: 10.1038/ng1127. Epub 2003 Mar 24.
Cultured primary human cells inevitably enter a state of replicative senescence for which the specific molecular trigger is unknown. We show that the single-strand telomeric overhang, a key component of telomere structure, is eroded at senescence. Expression of telomerase prevents overhang loss, suggesting that this enzyme prevents senescence by maintaining proper telomere structure. In contrast, progressive overhang loss occurs in cells that avoid senescence through the inactivation of p53 and Rb, indicating that overhang erosion is the result of continuous cell division and not a consequence of senescence. We thus provide evidence for a specific molecular alteration in telomere structure at senescence and suggest that this change, rather than overall telomere length, serves to trigger this state.
培养的原代人细胞不可避免地会进入复制性衰老状态，其具体的分子触发因素尚不清楚。我们发现，端粒结构的关键组成部分——单链端粒悬突在衰老过程中会被侵蚀。端粒酶的表达可防止悬突丢失，这表明该酶通过维持适当的端粒结构来防止衰老。相反，在通过p53和Rb失活而避免衰老的细胞中会发生渐进性悬突丢失，这表明悬突侵蚀是连续细胞分裂的结果，而非衰老的后果。因此，我们为衰老时端粒结构的特定分子改变提供了证据，并表明这种变化而非端粒的整体长度，是触发这种状态的原因。
