Implication of Dietary Iron-Chelating Bioactive Compounds in Molecular Mechanisms of Oxidative Stress-Induced Cell Ageing

Alexandra Barbouti; Nefeli Lagopati; Dimitris Veroutis; Vlasios Goulas; Konstantinos Evangelou; Panagiotis Kanavaros; Vassilis G Gorgoulis; Dimitrios Galaris

doi:10.3390/antiox10030491

Implication of Dietary Iron-Chelating Bioactive Compounds in Molecular Mechanisms of Oxidative Stress-Induced Cell Ageing

Antioxidants (Basel). 2021 Mar 21;10(3):491. doi: 10.3390/antiox10030491.

Authors

Alexandra Barbouti¹, Nefeli Lagopati², Dimitris Veroutis², Vlasios Goulas³, Konstantinos Evangelou², Panagiotis Kanavaros¹, Vassilis G Gorgoulis^{2

4

5

6}, Dimitrios Galaris⁷

Affiliations

¹ Department of Anatomy-Histology-Embryology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
² Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Faculty of Medicine, School of Health Science, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, 11527 Athens, Greece.
³ Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, 3036 Lemesos, Cyprus.
⁴ Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece.
⁵ Faculty of Biology, Medicine and Health Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, UK.
⁶ Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
⁷ Laboratory of Biological Chemistry, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.

Abstract

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as "lipofuscin," "ceroid," or "age pigment" is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe²⁺) ("labile iron"), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO^•) or alcoxyl (RO^•) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing.

Keywords: Mediterranean diet; ageing mechanisms; bioactive dietary compounds; cellular senescence; free radicals; iron-chelating agents; labile iron; oxidative stress.

Publication types

Review