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

Mariana Andrawus, Lital Sharvit, Noga Touitou, Batia Lerrer, Haim Y. Cohen, Gil Atzmon

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)7922-7932
Number of pages11
JournalAging
Volume15
Issue number16
DOIs
StatePublished - 28 Aug 2023

Keywords

  • aging
  • copy number variation
  • gene expression
  • pregnancy

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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