The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target

Weichao Huang; Zilong Zhang; Manuel Colucci; Linghui Deng; Mi Yang; Xinyi Huang; Xianghong Zhou; Yumin Jin; Edoardo Lazzarini; Carolina Balbi; Oriol Juanola; Aurora Valdata; Silvia Bressan; Yu Zhan; Fang Qi; Qiang Wei; Lu Yang; Xiaoli Zou; Shi Qiu

doi:10.1016/j.envint.2024.108447

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target

Environ Int. 2024 Feb:184:108447. doi: 10.1016/j.envint.2024.108447. Epub 2024 Jan 17.

Authors

Weichao Huang¹, Zilong Zhang¹, Manuel Colucci², Linghui Deng³, Mi Yang⁴, Xinyi Huang⁴, Xianghong Zhou⁵, Yumin Jin⁵, Edoardo Lazzarini⁶, Carolina Balbi⁷, Oriol Juanola⁸, Aurora Valdata⁹, Silvia Bressan¹⁰, Yu Zhan¹¹, Fang Qi¹², Qiang Wei⁵, Lu Yang¹³, Xiaoli Zou¹⁴, Shi Qiu¹⁵

Affiliations

¹ Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China; National Clinical Research Center of Geriatrics, The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
² Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), CH6500 Bellinzona, Switzerland; Università della Svizzera Italiana, CH6900 Lugano, Switzerland; Faculty of Biology and Medicine, University of Lausanne UNIL, CH1011 Lausanne, Switzerland.
³ National Clinical Research Center of Geriatrics, The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China; Department of Gerontology, West China Hospital of Sichuan University, Chengdu, China.
⁴ Department of Sanitary Technology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁵ Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.
⁶ Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano Switzerland.
⁷ Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Center for Molecular Cardiology, Zurich, Switzerland.
⁸ Gastroenterology and Hepatology, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
⁹ Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), CH6500 Bellinzona, Switzerland; Università della Svizzera Italiana, CH6900 Lugano, Switzerland; Department of Health Sciences and Technology (D-HEST) ETH Zurich, Zurich, CH, Switzerland.
¹⁰ Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), CH6500 Bellinzona, Switzerland; Università della Svizzera Italiana, CH6900 Lugano, Switzerland.
¹¹ Department of Environmental Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
¹² Department of Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China.
¹³ Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
¹⁴ Department of Sanitary Technology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. Electronic address: [email protected].
¹⁵ Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China; Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), CH6500 Bellinzona, Switzerland. Electronic address: [email protected].

PMID: 38246039
DOI: 10.1016/j.envint.2024.108447

Abstract

Introduction: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear.

Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways.

Results: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched.

Conclusion: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Keywords: AGE-RAGE signaling pathway; Biological age; Endocrine-disrupting chemical; Paraben; Phthalate.

MeSH terms

Aging
Cross-Sectional Studies
Endocrine Disruptors* / toxicity
Humans
Nutrition Surveys
Vitamins

Substances

Endocrine Disruptors
Vitamins