Improving understanding of ferroptosis: Molecular mechanisms, connection with cellular senescence and implications for aging
Diego De Leon-Oliva,
Diego Liviu Boaru,
Ana M. Minaya-Bravo,
Patricia De Castro-Martinez,
Oscar Fraile-Martinez,
Cielo Garcia-Montero,
David Cobo-Prieto,
Silvestra Barrena-Blázquez,
Laura Lopez-Gonzalez,
Agustín Albillos,
Melchor Alvarez-Mon,
Miguel A. Saez,
Raul Diaz-Pedrero,
Miguel A. Ortega
Affiliations
Diego De Leon-Oliva
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
Diego Liviu Boaru
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
Ana M. Minaya-Bravo
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
Patricia De Castro-Martinez
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
Oscar Fraile-Martinez
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
Cielo Garcia-Montero
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain
David Cobo-Prieto
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Immune System Diseases-Rheumatology Service, Central University Hospital of Defence-UAH Madrid, 28801, Alcala de Henares, Spain
Silvestra Barrena-Blázquez
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Universitary Hospital, Alcala de Henares, Spain
Laura Lopez-Gonzalez
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
Agustín Albillos
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Gastroenterology and Hepatology Service, Ramón y Cajal University Hospital, University of Alcalá, IRYCIS, Network Biomedical Research Center for Liver and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain
Melchor Alvarez-Mon
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, 28806, Alcala de Henares, Spain
Miguel A. Saez
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801, Alcala de Henares, Spain
Raul Diaz-Pedrero
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Universitary Hospital, Alcala de Henares, Spain; Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
Miguel A. Ortega
Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034, Madrid, Spain; Corresponding author. Department of Medicine and Medical Specialities, (CIBERehd), Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain.
In the face of cell damage, cells can initiate a response ranging from survival to death, the balance being crucial for tissue homeostasis and overall health. Cell death, in both accidental and regulated forms, plays a fundamental role in maintaining tissue homeostasis. Among the regulated mechanisms of cell death, ferroptosis has garnered attention for its iron-dependent phospholipid (PL) peroxidation and its implications in aging and age-related disorders, as well as for its therapeutic relevance. In this review, we provide an overview of the mechanisms, regulation, and physiological and pathological roles of ferroptosis. We present new insights into the relationship between ferroptosis, cellular senescence and aging, emphasizing how alterations in ferroptosis pathways contribute to aging-related tissue dysfunction. In addition, we examine the therapeutic potential of ferroptosis in aging-related diseases, offering innovative insights into future interventions aimed at mitigating the effects of aging and promoting longevity.
