TY - JOUR
T1 - Copy number variation as a tool for implementing pregnancy as an aging model
AU - Andrawus, Mariana
AU - Sharvit, Lital
AU - Touitou, Noga
AU - Lerrer, Batia
AU - Cohen, Haim Y.
AU - Atzmon, Gil
N1 - Publisher Copyright:
© 2023 Andrawus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - aging
KW - copy number variation
KW - gene expression
KW - pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85169847080&partnerID=8YFLogxK
U2 - 10.18632/aging.204936
DO - 10.18632/aging.204936
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C2 - 37639552
AN - SCOPUS:85169847080
SN - 1945-4589
VL - 15
SP - 7922
EP - 7932
JO - Aging
JF - Aging
IS - 16
ER -