2. Academic Validation
  3. Bisphenol S decreased lifespan and healthspan via insulin/IGF-1-like signaling-against mitochondrial stress in Caenorhabditis elegans

Bisphenol S decreased lifespan and healthspan via insulin/IGF-1-like signaling-against mitochondrial stress in Caenorhabditis elegans

  • Ecotoxicol Environ Saf. 2024 Oct 15:285:117136. doi: 10.1016/j.ecoenv.2024.117136.
Wenmiao He 1,  Zhiwei Liu 2,  Hongchao Zhang 3,  Qian Liu 2,  Zhenkun Weng 4,  Dongmei Wang 5,  Wenhui Guo 2,  Jin Xu 2,  Dayong Wang 6,  Zhaoyan Jiang 3,  Aihua Gu 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, China.
  • 2 State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, China.
  • 3 Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200000, China.
  • 4 State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, China; The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou Medical Center, Nanjing Medical University, China.
  • 5 The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou Medical Center, Nanjing Medical University, China.
  • 6 Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, China. Electronic address: dayongw@seu.edu.cn.
  • 7 State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: aihuagu@njmu.edu.cn.
PMID: 39353373 DOI: 10.1016/j.ecoenv.2024.117136
Abstract

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the Insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.

Keywords

Bisphenol S; C. elegans; Healthspan; Lifespan; Quercetin.

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