Pre-eclampsia is strongly associated with oxidative stress.

Using a systems approach, we bring together ideas surrounding cellular senescence and the role of senotherapeutics.

Small molecules such as ergothioneine can interact with the redox-sensitive transcription factor Nrf2.

The odds ratio against suffering early or late pre-eclampsia are massively decreased in those whose plasma ergothioneine are in the top 10 percentiles.

This analysis explains why.

Cellular senescence is a well-established biological phenomenon in eukaryotes. It involves DNA damage, telomere shortening, a senescence-associated secretory phenotype (SASP), and the inability of cells to replicate. It is associated with ageing, and also with oxidative stress. Given the importance of oxidative stress in pre-eclampsia, there is considerable evidence, that we review, that senescence plays an important role in both normal placental development and in the development of both early- and late-term pre-eclampsia. Autophagy is capable of delaying or even reversing the development of senescence, and certain small molecules such as sulforaphane and spermidine can stimulate autophagy, including via the redox-sensitive transcription factor Nrf2. Ergothioneine is a thiohistidine antioxidant that is protective against a variety of cardiovascular and other diseases. Ergothioneine also interacts with Nrf2, and pre-eclampsia occurs far less frequently in individuals with higher plasma ergothioneine levels. Together, these elements provide a self-consistent, molecular and systems biology explanation for at least one mechanism by which ergothioneine may be protective against pre-eclampsia.

Blood stasis

Clotting

Amyloid

Fibrinaloid

Senescence

Autophagy

Bioactive molecules

Senolytics

Inflammation

Spermidine

Ergothioneine

© 2025 The Author(s). Published by Elsevier B.V.