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A conserved regulatory architecture stabilizes cellular senescence across distinct triggers in human fibroblasts.

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Τίτλος: A conserved regulatory architecture stabilizes cellular senescence across distinct triggers in human fibroblasts.
Συγγραφείς: Shahzaib M; Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Luigi Vanvitelli Campania University, 80138, Naples, Italy., Aprile D; Department of Life Sciences, Health and Health Professions, Link Campus University, 00165, Rome, Italy., Squillaro T; Department of Life Sciences, Health and Health Professions, Link Campus University, 00165, Rome, Italy., Alessio N; Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Luigi Vanvitelli Campania University, 80138, Naples, Italy., Peluso G; Faculty of Medicine and Surgery, Saint Camillus International, University of Health Sciences, Rome, Italy., Di Bernardo G; Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Luigi Vanvitelli Campania University, 80138, Naples, Italy. gianni.dibernardo@unicampania.it., Galderisi U; Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Luigi Vanvitelli Campania University, 80138, Naples, Italy. umberto.galderisi@unicampania.it.; Sbarro Health Research Organization, Temple University, Philadelphia, PA, 19122, USA. umberto.galderisi@unicampania.it.; Genome and Stem Cell Center (GENKÖK), Erciyes University, Kayseri, Turkey. umberto.galderisi@unicampania.it.
Πηγή: GeroScience [Geroscience] 2026 Jun; Vol. 48 (3), pp. 3511-3529. Date of Electronic Publication: 2026 May 07.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE
Imprint Name(s): Original Publication: Cham : Springer International Publishing, [2017]-
Ιατρικοί όροι (MeSH): Cellular Senescence*/genetics , Cellular Senescence*/physiology , Fibroblasts*/metabolism , Fibroblasts*/physiology, Humans ; Protein Interaction Maps
Περίληψη: Cellular senescence arises through replicative exhaustion or acute stress, yet whether these distinct triggers share a reproducible transcriptional organization has remained unresolved. Seven public human fibroblast RNA-seq datasets were integrated across both trigger types, moving from differential expression through Gene Ontology and Reactome enrichment to protein-protein interaction network embedding within a single harmonized framework. Both triggers converged on concordant repression of replication and chromatin programs alongside induction of inflammatory and extracellular matrix outputs. Cross-trigger combination identified 263 commonly repressed and 112 commonly induced GO terms, with consistently higher enrichment scores in the repressed set, and 145 versus 13 shared Reactome pathways. Conserved induction of calcium ion homeostasis and membrane potential regulation, and conserved repression of RHO GTPase-Formin signaling, extended the shared program beyond canonical SASP biology into dimensions not previously described in human fibroblasts. Interactome embedding, applied here for the first time in a cross-trigger senescence framework, identified ten genes occupying both induced and repressed neighborhoods simultaneously, a structural layer invisible to enrichment analysis alone. ELAVL1 coordinates SASP output and growth arrest post-transcriptionally, while suppressed PARP1 alongside active ATM defines a self-reinforcing damage configuration. These results provide a quantitative cross-study reference and a structured basis for senotherapeutic candidate prioritization.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethics approval: Not applicable. Conflict of interest: The authors declare no competing interests.
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Grant Information: B53D23011280006 Ministero dell'Istruzione, dell'Università e della Ricerca
Contributed Indexing: Keywords: Cellular senescence; Gene Ontology; Human fibroblasts; Network biology; Reactome; Transcriptomics
Entry Date(s): Date Created: 20260507 Date Completed: 20260714 Latest Revision: 20260726
Update Code: 20260726
PubMed Central ID: PMC13356186
DOI: 10.1007/s11357-026-02297-6
PMID: 42096035
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2509-2723
DOI:10.1007/s11357-026-02297-6