Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies

Abstract

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

Keywords: age-related disease; copper; cuproptosis; mitochondria; protein lipid acylation.