von Zglinicki Thomas
Dept Gerontology, University of Newcastle, Wolfson Research Centre, General Hospital, Newcastle upon Tyne, UK.
Trends Biochem Sci. 2002 Jul;27(7):339-44. doi: 10.1016/s0968-0004(02)02110-2.
Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
大多数人类细胞中的端粒会随着每一轮DNA复制而缩短,因为它们缺乏端粒酶。然而,这并不是端粒DNA丢失速率的唯一决定因素。与染色体的其他部位相比,端粒DNA中的氧化损伤修复效果较差,氧化应激会加速端粒丢失,而抗氧化剂则会减缓端粒丢失。我在此提出,氧化应激是端粒丢失的重要调节因子,端粒驱动的复制性衰老主要是一种应激反应。这可能是进化而来的,以阻止暴露于高突变风险的细胞生长。
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