Center of Human Development and Aging (F-464 MSB), New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Ave, Newark, NJ, 07103, USA.
Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Sci Rep. 2021 Mar 4;11(1):5115. doi: 10.1038/s41598-021-84728-2.
Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.
最近的假说提出，人类胎盘和绒毛膜羊膜（CAM）经历端粒长度（TL）介导的衰老。这些假说基于平均 TL（mTL）测量值，但复制性衰老是由短的和功能失调的端粒引发的，而不是 mTL。我们通过一种先锋方法，端粒最短长度测定法，以及在 18 孕周至足月时在胎盘和 CAM 中测量端粒功能障碍诱导的 DNA 损伤焦点（TIF），来测量短端粒。胎盘和 CAM 都显示出短端粒和 TIF 的积累，但 mTL 从 18 周到足月并没有缩短。在胎盘，TIF 与短端粒相关，但与 mTL 无关。伴有羊膜内感染的早产妊娠的 CAM 显示出更短的 mTL 和增加的短端粒比例。我们的结论是，胎盘和可能的 CAM 经历 TL 介导的复制性衰老。是否 TL 介导的复制性衰老在所有早产中都起作用，需要进一步研究。
