Zsuzsa Muszka 1,2,4 , Viktória Jenei1,3,4, Rebeka Mácsik1 , Evgeniya Mezhonova1 , Silina Diyab1 , Réka Csősz1 , Attila Bácsi1 , Anett Mázló1✉ and Gábor Koncz 1 ✉
Chronic diseases affecting the cardiovascular system, diabetes mellitus, neurodegenerative diseases, and various other organspecific conditions, involve different underlying pathological processes. However, they share common risk factors that contribute to the development and progression of these diseases, including air pollution, hypertension, obesity, high cholesterol levels, smoking and alcoholism. In this review, we aim to explore the connection between four types of diseases with different etiologies and various risk factors. We highlight that the presence of risk factors induces regulated necrotic cell death, leading to the release of damage-associated molecular patterns (DAMPs), ultimately resulting in sterile inflammation. Therefore, DAMP-mediated inflammation may be the link explaining how risk factors can lead to the development and maintenance of chronic diseases. To explore these processes, we summarize the main cell death pathways activated by the most common life-threatening risk factors, the types of released DAMPs and how these events are associated with the pathophysiology of diseases with the highest mortality.
Cell Death and Disease (2025) 16:273 ; https://doi.org/10.1038/s41419-025-07563-7
FACTS
Environmental, physiological or behavioral risk factors can induce regulated necrotic cell death and DAMP production.
DAMP-related sterile inflammation plays a role in the development and progression of cardiovascular diseases, neurodegenerative diseases, diabetes or alcoholic and non-alcoholic liver diseases.
Current anti-inflammatory treatments do not target the root cause of cell death processes and the release of DAMPs.
OPEN QUESTIONS
To what extent can the harmful effects of risk factors be mitigated by regulating necrotic cell death?
To what extent do the DAMP patterns of pathologies associated with sterile inflammation overlap?
In which diseases can drugs targeting the pathomechanism ofsterile inflammation be used, such as drugs that inhibit the effects of regulated cell death or DAMPs?
1 Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 2 Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 3 Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 4 These authors contributed equally: Zsuzsa Muszka, Viktória Jenei. ✉email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 Edited By Massimiliano Agostini
Brigitte DRÉNO1 Isabelle BENOIT2 Eric PERRIER2 Miroslav RADMAN3
1 INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes Université, Nantes, France
2 NAOS-ILS, Aix-en-Provence, France,
3 Mediterranean Institute for Life Sciences, Split, Croatia, Naos Institute for Life Sciences, Aix-en-Provence, France, Université R.-Descartes Paris-5, Faculté de Médecine, INSERM U1, Paris, France
Reprints: Brigitte Dréno<该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。> <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Isabelle Benoit <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Eric Perrier <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chrono-logical and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slow-ing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.
Keywords: proteome, proteostasis, protein carbonylation, skin aging
his article is excerpted from the《Journal of Cosmetic Dermatology》by Wound World
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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