Integrated Multiomics Analysis and Mendelian Randomization Identify SIRT1 as a Pivotal Aging-Associated Gene in Meningioma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41208649", "kind": "science-record", "revision": 3, "content_hash": "sha256:250324691c1fd709e56ba897a7e1136311127757212cc70b6516d184a7094d4e", "created_at": "2026-11-01T20:31:14Z", "updated_at": "2026-11-01T22:14:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Multiomics Analysis and Mendelian Randomization Identify SIRT1 as a Pivotal Aging-Associated Gene in Meningioma.", "doi": "10.1002/iub.70072", "pmid": "41208649", "authors": ["Guangyu Du", "Daikang Xu", "Jingxian Sun", "Shusheng Che", "Junwei Ma", "Xiaolei Lan", "Jianpeng Wang", "Zhiyong Yan"], "journal": "IUBMB life", "year": 2025, "abstract": "Meningiomas (MGMs) are the most prevalent benign intracranial tumors in adults, with incidence markedly increasing with age, underscoring the need to explore aging-associated molecular mechanisms. In this study, we integrated transcriptomic datasets (GSE43290, GSE54934, GSE77259, and GSE183655) from the GEO database and aging-related genes (ARGs) from the Human Aging Genomic Resources to identify key genes implicated in MGM. We screened differentially expressed ARGs (ARG-DEGs) and conducted GO and KEGG pathway enrichment analyses, revealing significant involvement in cancer-related processes, viral infection pathways, and the FoxO signaling pathway. Using LASSO, SVM, CytoHubba-MCC, and MCODE algorithms, we identified two hub ARGs, SIRT1 and CEBPB. Immune infiltration analysis via ssGSEA indicated notable alterations in B cells, neutrophils, helper T cells, and regulatory T cells between MGM and healthy tissues, all closely associated with the hub genes. Furthermore, construction of a miRNA-TF-mRNA regulatory network highlighted the complex upstream regulation of these genes. Mendelian randomization analysis supported a potential causal relationship between SIRT1 and MGM development. Single-cell RNA sequencing data further confirmed heterogeneous expression of SIRT1 across key cell populations within MGM, brain-tumor interface, and dura mater tissues. These findings were validated through qRT-PCR and Western blot analyses, which demonstrated significant differences in SIRT1 expression at both the transcript and protein levels. Collectively, our study reveals that aging and immune dysregulation contribute to MGM pathogenesis and highlights SIRT1, in particular, as a potential diagnostic biomarker and therapeutic target, offering new insights into age-related mechanisms underlying MGM.", "claims": [{"id": "claim-method", "statement": "In this study, we performed two‐sample MR analysis using the “TwoSampleMR” R package to assess the causal relationship between key ARG‐DEGs and MGMs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41208649", "locator": "sections[10] \"MR Analysis Clarified the Causal Relationship Between Key ARG‐DEGs and MGM\" paragraph 2", "quote": "In this study, we performed two‐sample MR analysis using the “TwoSampleMR” R package to assess the causal relationship between key ARG‐DEGs and MGMs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41208649", "locator": "sections[37] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SIRT1 was identified as a key aging-related gene associated with meningioma pathogenesis, with supporting Mendelian randomization evidence and validation at the transcript and protein levels.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41208649", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Collectively, our study reveals that aging and immune dysregulation contribute to MGM pathogenesis and highlights SIRT1, in particular, as a potential diagnostic biomarker and therapeutic target, offering new insights into age‐related mechanisms underlying MGM."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SIRT1 was identified as a key aging-related gene associated with meningioma pathogenesis, with supporting Mendelian randomization evidence and validation at the transcript and protein levels.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41208649"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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