Bisphenol S reduces lifespan and health by affecting insulin-like signaling against mitochondrial stress in roundworms

Exposure to Bisphenol S (BPS) at environmentally relevant doses significantly decreased lifespan and healthspan in C. elegans.

• Both early-life and whole-life exposure to BPS at doses of 0.6, 6, and 60 μg/L is associated with reduced lifespan and healthspan.
• BPS exposure impaired mitochondrial structure and function, leading to increased production of reactive oxygen species (ROS) and oxidative stress.
• Increased expression of insulin/IGF-like signaling (IIS) was observed following BPS exposure, alongside inhibition of the IIS transcription factor daf-16 and its downstream anti-oxidative genes.
• Quercetin was shown to improve oxidative stress caused by BPS by reversing changes in the IIS/daf-16 signaling pathway.
• The effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and gene expressions were reversed in daf-2 and daf-16 mutants, indicating the importance of the IIS/daf-16 pathway in aging regulation.
• Molecular simulations confirmed a stable interaction between DAF-2 and BPS, which was diminished by quercetin.

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