GeroScience Study Reports Escitalopram Accelerates Aging via IIS and Autophagy Impairment

Researchers found that the antidepressant escitalopram accelerates biological aging in model organisms and human cells by disrupting the conserved IIS/autophagy pathway, suggesting potential safety risks with long-term use.

A study published in GeroScience reported that the administration of escitalopram at juvenile, young, or old adult stages significantly shortens lifespan and impairs healthspan in Caenorhabditis elegans.

The administration of escitalopram was shown to increase lipofuscin accumulation, reduce stress resistance, and induce mitochondrial dysfunction marked by elevated reactive oxygen species (ROS) production and diminished membrane potential.

In human BJ fibroblasts, escitalopram triggered premature cellular senescence, indicated by increased SA-β-gal activity and upregulated P53/P21 expression, alongside impaired cell proliferation.

Genetic analyses in mutant worms established that the drug's pro-aging effects are mediated by the insulin/IGF-1 signaling (IIS) pathway, which leads to the subsequent suppression of autophagy.

While other selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, have been reported to extend lifespan, this study demonstrates that escitalopram has the opposite effect, indicating drug-specific differences within the same class.

The findings highlight a potential pro-aging toxicity for escitalopram with long-term use, especially given its status as a widely prescribed antidepressant.

Mechanistically, the cellular senescence observed in human cells was mediated by a failure in the fusion process between autophagosomes and lysosomes, identifying a specific cellular target for therapeutic rescue.

The divergent effects of SSRIs on longevity indicate a need for rigorous, longevity-focused toxicity screening during the pre-clinical development of psychiatric therapies.

This research highlights the clinical relevance of therapeutic platforms designed to restore autophagy or mitigate drug-induced mitochondrial dysfunction.

Further clinical or epidemiological evaluations to investigate whether long-term escitalopram use correlates with accelerated biological aging or biomarker changes in human cohorts.

Preclinical studies testing whether pharmacological autophagy enhancers can rescue the life- and healthspan deficits caused by escitalopram.