Sex differences in antioxidant defence and the regulation of redox homeostasis in physiology and pathology. (April 2023)

• Record Type: Journal Article
• Authors: Tiberi, Jessica; Cesarini, Valeriana; Stefanelli, Roberta; Canterini, Sonia; Fiorenza, Maria Teresa; La Rosa, Piergiorgio
• Is Part Of: Mechanisms of ageing and development. Volume 211(2023)
• Publication Date: 2023-04
• Subjects: Sex-differences -- Oxidative Stress -- NRF2 -- Gender -- Antioxidant defence; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2023.111802
• Languages: English
• ISSNs: 0047-6374

Abstract

Abstract: Reactive oxygen species (ROS) is a term that defines a group of unstable compounds derived from exogenous sources or endogenous metabolism. Under physiological conditions, low levels of ROS play a key role in the regulation of signal transduction- or transcription-mediated cellular responses. In contrast, excessive and uncontrolled loading of ROS results in a pathological state known as oxidative stress (OS), a leading contributor to aging and a pivotal factor for the onset and progression of many disorders. Evolution has endowed cells with an antioxidant system involved in stabilizing ROS levels to a specific threshold, maintaining ROS-induced signalling function and limiting negative side effects. In mammals, a great deal of evidence indicates that females defence against ROS is more proficient than males, determining a longer lifespan and lower incidence of most chronic diseases. In this review, we will summarize the most recent sex-related differences in the regulation of redox homeostasis. We will highlight the peculiar aspects of the antioxidant defence in sex-biased diseases whose onset or progression is driven by OS, and we will discuss the molecular, genetic, and evolutionary determinants of female proficiency to cope with ROS. Highlights: Antioxidant defence controls ROS levels, limiting their negative effects and securing proper cellular signaling. Females exhibit a more proficient antioxidant defence, lower accumulation of ROS-induced damage over time, and longer lifespan. Processes increasing protection from ROS in females, confer resistance to the development of most chronic diseases. Genetic, molecular, and evolutionary features underlie sex-biased response to ROS and vulnerability to various diseases.