Role of Senescence in the Pathophysiology of Preeclampsia and Future Health

Apr 10, 2026Hypertension (Dallas, Tex. : 1979)

How Cell Aging May Contribute to Preeclampsia and Affect Long-Term Health

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Abstract

Preeclampsia affects up to 5% of pregnancies worldwide and is linked to long-term health risks.

Preeclampsia is associated with hypertension, systemic disease, and proteinuria during pregnancy.
It significantly increases the risk of future hypertension, cardiovascular disease, chronic kidney disease, and multimorbidity.
Different underlying mechanisms during pregnancy may influence the clinical presentation and future health outcomes of women with preeclampsia.
Cellular senescence may be a key mechanism linking preeclampsia to accelerated cardiovascular aging.
Evidence shows that preeclampsia is associated with increased senescence burden and dysfunction of mesenchymal stem cells.
Senolytic and senomorphic therapies are discussed as potential strategies for modifying disease outcomes in women with a history of preeclampsia.

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Preeclampsia is a pregnancy-specific hypertensive disorder affecting up to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality globally. It is increasingly recognized that preeclampsia, from both clinical and pathophysiological standpoints, is a heterogeneous disease and that several mechanisms may lead to a clinical syndrome of hypertension, systemic disease, and proteinuria. Beyond its acute obstetric consequences, preeclampsia confers a significantly increased risk of future hypertension, cardiovascular disease, chronic kidney disease, and multimorbidity. Distinct underlying pathological mechanisms at the time of pregnancy may not only define clinical presentation and subtype of preeclampsia but may also make varying contributions to future cardiovascular and kidney disease. Emerging evidence implicates cellular senescence, a state of irreversible cell-cycle arrest accompanied by a proinflammatory senescence-associated secretory phenotype, as one of the mechanisms of preeclampsia that may serve as a mechanistic link between preeclampsia, accelerated cardiovascular aging, and future cardiovascular and kidney disease. This review synthesizes current evidence supporting the role of senescence in the pathophysiology of preeclampsia, demonstrated as accelerated epigenetic aging, increased senescence burden, and mesenchymal stem cell dysfunction, and discusses how persistence of senescence and propagation of senescent cells may contribute to vascular dysfunction decades after affected pregnancies. We further explore the translational implications of senolytic and senomorphic therapies as potential disease-modifying strategies in women with a history of preeclampsia.

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Role of Senescence in the Pathophysiology of Preeclampsia and Future Health

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