ArticleAging cell2021
Advanced maternal age causes premature placental senescence and malformation via dysregulated α-Klotho expression in trophoblasts.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 72 citations in OpenAlex.
- Elevated contractility drives implantation failure in mouse embryos from aged females.Nature cell biology · 2026Article
- Age-Associated Senescence of Decidual Macrophages: A Key Mediator of Adverse Pregnancy Outcomes in Advanced Maternal Age.Aging cell · 2026Article
- Aberrant expression of Gremlin1 induces trophoblast senescence in the placenta of advanced maternal age pregnancy.Journal of translational medicine · 2026Article
- KLOTHO Deficiency Drives Ovarian Aging by Inducing Granulosa Cell Senescence and Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Placental and fetal consequences of maternal selective serotonin reuptake inhibitor use: current evidence and unresolved questions.Frontiers in pharmacology · 2026Review
- Late-Onset Preeclampsia is characterised by Accelerated Placental Aging.bioRxiv : the preprint server for biology · 2025Article
- A mechanical origin for implantation defects in embryos from aged females.bioRxiv : the preprint server for biology · 2025Article
- Article
- High-Risk Outcomes in In Vitro Fertilization Pregnancies for Women of a Very Advanced Maternal Age: Insights from a Multi-Hospital Study in Greece.Journal of clinical medicine · 2025Article
- Placental trophoblast aging in advanced maternal age is related to increased oxidative damage and decreased YAP.Frontiers in cell and developmental biology · 2025Article
- High-throughput sequencing unravels placental vascular dysfunction and oxidative stress as mechanistic drivers of advanced maternal age-associated pregnancy.Frontiers in genetics · 2025Article
- Melatonin Attenuates PFOS-Induced Reproductive Toxicity of Pregnant Mice due to Placental Damage Via Antioxidant, Anti-Aging and Anti-Inflammatory Pathways.Birth defects research · 2024Article
- The updated understanding of advanced maternal age.Fundamental research · 2024Review
- Trends in maternal ICU admissions at a quaternary centre in Montreal, Canada, and impact of maternal age on critical care outcomes.Obstetric medicine · 2024Article
- Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study.BMC pregnancy and childbirth · 2024Article
- The associations of gestational weight gain and midpregnancy lipid levels with placental size and placental-to-birth weight ratio: findings from a chinese birth cohort study.BMC pregnancy and childbirth · 2023Article
- Fetal abdominal obesity and the ensuing adverse perinatal outcomes in older obese pregnant women with or without obesity and with normal glucose tolerance.Scientific reports · 2023Review
- DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion.Clinical epigenetics · 2023Article
- Article
- An Evaluation of Exposure to 18 Toxic and/or Essential Trace Elements Exposure in Maternal and Cord Plasma during Pregnancy at Advanced Maternal Age.International journal of environmental research and public health · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advanced maternal age (AMA) pregnancy is associated with higher risks of adverse perinatal outcomes, which may result from premature senescence of the placenta. α-Klotho is a well-known antiaging protein; however, its expression and effect on the placenta in AMA pregnancies have not yet been fully elucidated. The expression patterns of α-Klotho in mouse and human placentas from AMA pregnancies were determined by Western blotting and immunohistochemistry (IHC) staining. α-Klotho expression in JAR cells was manipulated to investigate its role in trophoblastic senescence, and transwell assays were performed to assess trophoblast invasion. The downstream genes regulated by α-Klotho in JAR cells were first screened by mRNA sequencing in α-Klotho-knockdown and control JAR cells and then validated. α-Klotho-deficient mice were generated by injecting klotho-interfering adenovirus (Ad-Klotho) via the tail vein on GD8.5. Ablation of α-Klotho resulted in not only a senescent phenotype and loss of invasiveness in JAR cells but also a reduction in the transcription of cell adhesion molecule (CAM) genes. Overexpression of α-Klotho significantly improved invasion but did not alter the expression of senescence biomarkers. α-Klotho-deficient mice exhibited placental malformation and, consequently, lower placental and fetal weights. In conclusion, AMA results in reduced α-Klotho expression in placental trophoblasts, therefore leading to premature senescence and loss of invasion (possibly through the downregulation of CAMs), both of which ultimately result in placental malformation and adverse perinatal outcomes.
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