2025/07/18 by Douglas B. Kell, Loren Kell, Louise C. Kenny +3 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Genomics, phytochemicals, and oxidative stress #Circadian rhythm and melatonin #Epigenetics and DNA Methylation
paper · doi:10.1016/j.jri.2025.104621
openalex publication_date 2025/07/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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. • 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.