Accelerated Vascular Aging in Women with Prior Preeclampsia: A Review of Epidemiology, Pathophysiological Mechanisms, and Geroprotective Strategies

TL;DR

Women who had preeclampsia show signs of faster aging in multiple body systems, suggesting a need for new strategies to prevent long-term health issues.

Contribution

This paper introduces a novel framework linking preeclampsia to accelerated aging through shared molecular pathways and proposes geroprotective strategies.

Findings

Women with prior preeclampsia show a 1.5-year acceleration in reproductive aging based on AMH levels.

Preeclampsia is linked to a twofold increase in cardiovascular disease risk and earlier onset of hypertension.

Shared pathways like mitochondrial dysfunction and inflammation connect preeclampsia and ovarian aging.

Abstract

Preeclampsia (PE) has traditionally been regarded as a pregnancy-limited hypertensive disorder; however, accumulating evidence increasingly positions it as a pivotal early-life vascular stress test that manifests underlying vulnerabilities and accelerates biological aging. Women with a history of PE exhibit a heightened susceptibility to premature-onset multi-systemic diseases, specifically cardiovascular, ovarian, renal, and metabolic decline. This suggests that PE acts as a catalyst for accelerated aging, driven by shared pathophysiological pathways that represent common mechanisms of systemic senescence. This review provides a comprehensive analysis of the epidemiological links and pathogenic drivers underpinning accelerated systemic aging following PE, with a specific focus on the cardiovascular-ovarian axis. Epidemiological data consistently demonstrate that women with prior PE exhibit significantly reduced anti-Müllerian hormone (AMH) levels, translating to an estimated 1.5-year acceleration in reproductive aging. In parallel, PE is associated with a twofold increase in lifetime cardiovascular disease (CVD) risk and the onset of chronic hypertension occurring an average of 7.7 years earlier. However, reconciling the phenotypic heterogeneity of PE and transcending the constraints of non-experimental designs are essential for firmly establishing this accelerated aging paradigm. At the molecular level, PE and ovarian aging converge on shared pathways—including mitochondrial dysfunction, oxidative stress, inflammation, and epigenetic dysregulation—collectively defining a distinct pathogenic ovarian–vascular aging axis. Proposed geroscience-based strategies advocate for refined risk stratification by incorporating molecular aging biomarkers—such as epigenetic clocks and inflammatory profiles—alongside conventional clinical indicators. This integrative framework facilitates the early identification of high-risk aging phenotypes, enabling targeted monitoring and timely interventions to preemptively modulate accelerated aging pathways. Pharmacological approaches within this framework emphasize the judicious repurposing of established agents, such as metformin, statins, and SGLT2 inhibitors, while emerging gerotherapeutics, including senolytics and senomorphics, provide a conceptual foundation for targeting the fundamental biological drivers of senescence. Although these geroprotective strategies, including the repurposing of established agents and the use of senolytics, offer innovative conceptual frameworks for targeting the fundamental drivers of senescence, they remain largely exploratory and require further clinical validation. Such strategies offer novel opportunities to shift the clinical focus from treating isolated comorbidities to modulating the shared molecular substrates of aging, ultimately promoting healthy aging and functional longevity in the elderly female population.

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