Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort

Vanessa Schoissengeier; Lina Maqboul; Daniela Weber; Tilman Grune; Alexander Bürkle; Maria Moreno-Villaneuva; Claudio Franceschi; Miriam Capri; Jürgen Bernhard; Olivier Toussaint; Florence Debacq-Chainiaux; Birgit Weinberger; Efstathios S Gonos; Ewa Sikora; Martijn Dollé; Eugène Jansen; P Eline Slagboom; Antti Hervonnen; Mikko Hurme; Nicolle Breusing; Jan Frank; Andrew C Bulmer; Karl-Heinz Wagner

doi:10.1016/j.isci.2024.110234

Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort

iScience. 2024 Jun 9;27(7):110234. doi: 10.1016/j.isci.2024.110234. eCollection 2024 Jul 19.

Authors

Vanessa Schoissengeier^{1

2}, Lina Maqboul¹, Daniela Weber^{3

4}, Tilman Grune^{3

5

6}, Alexander Bürkle⁷, Maria Moreno-Villaneuva^{7

8}, Claudio Franceschi^{9

10}, Miriam Capri^{9

11}, Jürgen Bernhard¹², Olivier Toussaint¹³, Florence Debacq-Chainiaux¹³, Birgit Weinberger¹⁴, Efstathios S Gonos¹⁵, Ewa Sikora¹⁶, Martijn Dollé¹⁷, Eugène Jansen¹⁷, P Eline Slagboom¹⁸, Antti Hervonnen¹⁹, Mikko Hurme¹⁹, Nicolle Breusing²⁰, Jan Frank²¹, Andrew C Bulmer²², Karl-Heinz Wagner^{1

23}

Affiliations

¹ Department of Nutritional Sciences, University of Vienna, Vienna 1090, Austria.
² Vienna Doctoral School for Pharmaceutical, Nutritional and Sport Sciences (PhaNuSpo), University of Vienna, 1090 Vienna, Austria.
³ Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.
⁴ Food4Future (F4F), c/o Leibniz Institute of Vegetable and Ornamental Crops (IGZ), 14979 Grossbeeren, Germany.
⁵ German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
⁶ German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, 40225 Düsseldorf, Germany.
⁷ Molecular Toxicology Group, Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
⁸ Human Performance Research Centre, Department of Sport Science, University of Konstanz, 78464 Konstanz, Germany.
⁹ Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
¹⁰ Laboratory of Systems Medicine of Healthy Aging, Institute of Biology and Biomedicine and Institute of Information Technology, Mathematics and Mechanics, Department of Applied Mathematics, Lobachevsky State University, 603005 Nizhny Novgorod, Russia.
¹¹ Interdepartmental Center - Alma Mater Research Institute on Global Challenges and Climate Change - University of Bologna, 40126 Bologna, Italy.
¹² BioTeSys GmbH, 73728 Esslingen, Germany.
¹³ URBC-NARILIS, University of Namur, 5000 Namur, Belgium.
¹⁴ Institute for Biomedical Aging Research, Universität Innsbruck, 6020 Innsbruck, Austria.
¹⁵ National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 116 35 Athens, Greece.
¹⁶ Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 00-901 Warsaw, Poland.
¹⁷ Centre for Health Protection, National Institute for Public Health and the Environment, 3720BA Bilthoven, the Netherlands.
¹⁸ Department of Molecular Epidemiology, Leiden University Medical Centre, 2333 ZC Leiden, the Netherlands.
¹⁹ Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland.
²⁰ Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, 70599 Stuttgart, Germany.
²¹ Department of Food Biofunctionality, University of Hohenheim, 70599 Stuttgart, Germany.
²² School of Pharmacy and Medical Sciences, Griffith University, Gold Coast Campus, Brisbane, QLD, Australia.
²³ Research Platform Active Ageing, University of Vienna, Vienna 1090, Austria.

Abstract

Recent studies have shown that elevated concentrations of unconjugated bilirubin (UCB) may be a protective host factor against the development of noncommunicable diseases (NCDs), whereas low levels of UCB are associated with the opposite effect. The results of this European study, in which 2,489 samples were tested for their UCB concentration using high-performance liquid chromatography (HPLC) and additional data from the MARK-AGE database were used for analysis, provide further evidence that elevated UCB concentrations are linked to a lower risk of developing NCDs and may act as a predictive marker of biological aging as individuals with elevated UCB concentrations showed favorable outcomes in metabolic health and oxidative-stress-related biomarkers. These findings underline the significance of studying individuals with moderate hyperbilirubinemia and investigate UCB routinely, also in the setting of aging, since this condition affects millions of people worldwide but has been underrepresented in clinical research and practice until now.

Keywords: human metabolism; pathology; public health.