4.6 Article

Copy number variation as a tool for implementing pregnancy as an aging model

Journal

AGING-US
Volume 15, Issue 16, Pages 7922-7932

Publisher

IMPACT JOURNALS LLC

Keywords

aging; pregnancy; copy number variation; gene expression

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Copy number variations (CNV) play a significant role in genome variability and have been associated with aging and pregnancy physiology. By studying CNVs in pregnant mice, researchers have found that most of the selected CNVs showed an opposite trend during pregnancy and post-partum. Additionally, significant differential expression was observed in the nearby genes of the candidate CNVs. This study highlights the importance of using pregnancy as a model for aging and reveals the mechanisms and similarities between pregnancy and aging.
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 (APA2A, LSS, RBDHF1, PLAAT1, and SCL17A2), but not in the WSCD2 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.

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