{"title":"From Genome to Geroscience: How DNA Damage Shapes Systemic Decline","authors":"Athanasios Siametis, George A. Garinis","doi":"10.1002/bies.70051","DOIUrl":null,"url":null,"abstract":"<p>Persistent genomic instability compromises cellular viability while also triggers non-cell-autonomous responses that drive dysfunction across tissues, contributing to aging. Recent evidence suggests that DNA damage activates secretory programs, including the release of inflammatory cytokines, damage-associated molecular patterns, and extracellular vesicles, that reshape immune homeostasis, stem cell function, and metabolic balance. Although these responses may initially support tissue integrity and organismal survival, their chronic activation has been associated with tissue degenerative changes and systemic decline. Here, we discuss how nuclear DNA damage responses trigger the activation of cytoplasmic sensing pathways, promote secretory phenotypes, and affect organismal physiology. Targeting DNA damage-driven mechanisms may help buffer harmful systemic responses while preserving regeneration and immune surveillance, offering new ways to delay aging-related decline.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"47 10","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.70051","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioEssays","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bies.70051","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Persistent genomic instability compromises cellular viability while also triggers non-cell-autonomous responses that drive dysfunction across tissues, contributing to aging. Recent evidence suggests that DNA damage activates secretory programs, including the release of inflammatory cytokines, damage-associated molecular patterns, and extracellular vesicles, that reshape immune homeostasis, stem cell function, and metabolic balance. Although these responses may initially support tissue integrity and organismal survival, their chronic activation has been associated with tissue degenerative changes and systemic decline. Here, we discuss how nuclear DNA damage responses trigger the activation of cytoplasmic sensing pathways, promote secretory phenotypes, and affect organismal physiology. Targeting DNA damage-driven mechanisms may help buffer harmful systemic responses while preserving regeneration and immune surveillance, offering new ways to delay aging-related decline.
期刊介绍:
molecular – cellular – biomedical – physiology – translational research – systems - hypotheses encouraged
BioEssays is a peer-reviewed, review-and-discussion journal. Our aims are to publish novel insights, forward-looking reviews and commentaries in contemporary biology with a molecular, genetic, cellular, or physiological dimension, and serve as a discussion forum for new ideas in these areas. An additional goal is to encourage transdisciplinarity and integrative biology in the context of organismal studies, systems approaches, through to ecosystems, where appropriate.