1. Academic Validation
  2. Environmentally relevant concentrations of perfluorobutane sulfonate impair locomotion behaviors and healthspan by downregulating mitophagy in C. elegans

Environmentally relevant concentrations of perfluorobutane sulfonate impair locomotion behaviors and healthspan by downregulating mitophagy in C. elegans

  • J Hazard Mater. 2024 Sep 23:480:135938. doi: 10.1016/j.jhazmat.2024.135938.
Yahui Shang 1 Kelie Chen 2 Heng Ni 3 Xiaoyu Zhu 1 Xiaoyu Yuan 1 Yuwei Wang 1 Xinxin Liu 1 Zhenyan Cui 1 Yuequn Niu 4 Yu Shi 5 Han Wu 6 Dajing Xia 7 Yihua Wu 8
Affiliations

Affiliations

  • 1 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Pathology, University Hospital Bonn, Bonn, Germany.
  • 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 6 Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: doctorwuhan@zju.edu.cn.
  • 7 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: dxia@zju.edu.cn.
  • 8 Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: georgewu@zju.edu.cn.
Abstract

Perfluorobutane sulfonate (PFBS), a chemical compound within the group of per- and polyfluoroalkyl substances (PFAS), has been utilized as an alternative to perfluorooctane sulfonate (PFOS) recently. Previous research has indicated that PFBS might be linked to a range of health concerns. However, the potential impacts of environmentally relevant concentrations of PFBS (25 nM) on aging as well as the underlying mechanisms remained largely unexplored. In this study, we investigated the impact of PFBS exposure on aging and the associated mechanisms in Caenorhabditis elegans. Our findings indicated that exposure to PFBS impaired healthspan of C. elegans. Through bioinformatic screening analyses, we identified that the dysfunctions of pink-1 mediated Mitophagy might play a critical role in PFBS induced aging. The results furtherly revealed that PFBS exposure led to elevated levels of Reactive Oxygen Species (ROS) and Mitophagy impairment through downregulating pink-1/pdr-1 pathway. Furthermore, the Mitophagy agonist Urolithin A (UA) effectively reversed PFBS-induced Mitophagy dysfunction and enhanced healthspan in C. elegans. Taken together, our study suggested that exposure to environmentally relevant concentrations of PFBS could accelerate aging by downregulating the pink-1 mediated Mitophagy. Promoting Mitophagy within cells could be a promising therapeutic strategy for delaying PFBS-induced aging.

Keywords

Caenorhabditis elegans; Mitophagy; Perfluorobutane sulfonate; Reactive oxygen species; pink-1.

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