Department of Human Biology, University of Haifa, Haifa 3498838, Israel.
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Aging (Albany NY). 2023 Aug 28;15(16):7922-7932. doi: 10.18632/aging.204936.
Copy number variations (CNV) are a major contributor to genome variability and have been linked to aging and other degradable phenotypes such as pregnancy physiology. To demonstrate how pregnancy can be used as a model of aging, we used CNVs from pregnant mice. Candidate CNVs were selected by applying case-control analysis in human centenarians compared with control groups. These CNVs were aligned with the mouse genome and their copy variation was assessed using qRT-PCR in liver and blood tissue samples from pregnant mice throughout pregnancy (baseline; first, second, and third trimester; post-partum). Eight of the ten selected CNVs demonstrated a significant decline/increase trend throughout the pregnancy followed by opposite direction soon after delivery in the liver and blood of the mouse tissues. Furthermore, significant differential expression was detected among the candidate CNVs' close vicinity genes (, and ), but not in the gene. Establishing a genetic link between longevity and pregnancy is a significant step toward implementing the pregnancy process as a model for aging. These results in pregnant mice highlight the mechanism and similarities between pregnancy and aging. Investigating the mechanisms that cause such rejuvenation after labor could change our aging treatment paradigm.
拷贝数变异（CNV）是基因组变异的主要贡献者，与衰老和其他可降解表型（如妊娠生理）有关。为了证明妊娠如何可以作为衰老的模型，我们使用了来自妊娠小鼠的 CNV。通过将百岁老人与对照组进行病例对照分析，选择候选 CNV。将这些 CNV 与小鼠基因组进行比对，并使用 qRT-PCR 在妊娠小鼠的肝脏和血液组织样本中评估其在整个妊娠过程中的拷贝变化（基线；第一、第二和第三孕期；产后）。在妊娠过程中，十个选定的 CNV 中有八个表现出显著的下降/增加趋势，随后在小鼠组织的肝脏和血液中很快出现相反的趋势。此外，在候选 CNV 的附近基因（、和）中检测到显著的差异表达，但在基因中没有检测到。在长寿和妊娠之间建立遗传联系是朝着将妊娠过程作为衰老模型实施的重要一步。这些妊娠小鼠的结果突出了妊娠和衰老之间的机制和相似性。研究导致产后这种恢复活力的机制可能会改变我们的衰老治疗模式。
