Metal-sulfur metabolic derangement and regulated cell death in age-related cardiovascular diseases: mechanisms, biomarkers, and emerging interventions.

Authors

Jinqiao Li, Zijin Sun, Mingxuan Liu, Linjing Song, Kai Wang, Yalin Luo, Wenhao Jia, Yuanhui Hu, Ruxiu Liu, Xing Chang

Published in

Ageing research reviews. Pages 103360. Sep 05, 2026. Epub Sep 05, 2026.

Abstract

Cardiovascular ageing is accompanied by progressive impairment of redox buffering, mitochondrial quality control, proteostasis and metal homeostasis. Iron and copper homeostasis, together with cystine-glutathione and thiol/disulfide redox metabolism, are increasingly recognized as interconnected determinants of metabolic vulnerability and regulated cell death (RCD) in age-related cardiovascular diseases. Ferroptosis, defined by iron-dependent lipid peroxidation and impaired anti-peroxidative defence, has a substantial evidence base in myocardial ischaemia/reperfusion injury, atherosclerosis, heart failure and cardiac fibrosis. By contrast, cuproptosis is supported by emerging but still limited cardiovascular mechanistic evidence, whereas disulfidptosis in cardiovascular tissues is supported mainly by cross-system mechanistic extrapolation and pathway-associated transcriptomic signatures rather than demonstration of canonical cell-death execution. This review integrates iron-, copper-, and sulfur-metabolism-related RCD programmes across shared pathological interfaces, disease-specific contexts, and translational opportunities. We highlight circulating metal and thiol/disulfide indices, transcriptomic signatures, lesion-responsive nanomedicine, and imaging platforms as candidate routes for risk stratification and intervention. A layered interpretation of evidence is essential for translating iron-, copper-, and sulfur-metabolism-related RCD mechanisms into ageing-focused cardiovascular medicine. Here, "metal-sulfur metabolic derangement" is used as an evidence-stratified conceptual framework for partially intersecting stress programmes, not as a unitary mechanism or evidence that the three death modes have equivalent cardiovascular importance.

PMID:
42700865
Bibliographic data and abstract were imported from PubMed on 06 Sep 2026.

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