{ "api_version": "v1", "id": "srsf1-aging-safety-window-2026-11-02", "published_at": "2026-11-02", "publisher": "Darkoza Knowledge Lab / OERSI", "title": "SRSF1 and healthy aging: evidence-audited reanalysis and safety-window hypothesis", "evidence_status": "secondary computational reanalysis of originating preclinical study; hypothesis-generating; not independent biological replication", "original_discovery_claim": false, "clinical_evidence": false, "treatment_recommendation": false, "report": "https://darkoza.com/science/reports/srsf1-aging-safety-window/report.html", "report_markdown": "https://darkoza.com/science/reports/srsf1-aging-safety-window/report.md", "endpoint": "https://darkoza.com/science-api/v1/experiments/srsf1-aging-safety-window.json", "source_data": { "geo_series": "GSE325735", "geo_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325735", "article_doi": "10.1038/s43587-026-01234-8", "supplementary_workbook": "MOESM15", "mapping_sheet": "3a", "differential_expression_sheet": "3e", "crosswalk_qc": { "selected_aliases": 24, "unique_geo_metadata_matches": 24, "ambiguous": 0, "unmatched": 0, "status": "PASS" } }, "design": { "condition": "SRSF1 transgene vs mTagBFP2/BFP control; doxycycline 2000 ng/mL; 3 days", "independent_donor_lines": 6, "technical_replicates_per_group": 2, "raw_count_samples": 24, "analysis_unit": "donor-derived cell line; technical replicates averaged" }, "method": { "secondary_analysis": "targeted 18-gene panel; log2(CPM + 0.5); paired within-donor contrasts", "author_crosscheck": "published DESeq2 results from the same originating study supplementary table", "exploratory_sign_tests": "six donor lines; no multiple-testing correction; not confirmatory", "independent_biological_replication": false }, "selected_results": [ { "gene": "CXCL8", "label": "IL-8", "authors_fold_change": 4.9818, "authors_adjusted_p": 0.000010201, "ours_cpm_fold_change": 2.6132, "ours_directional_donors_up": 6, "ours_directional_donors_down": 0 }, { "gene": "CDKN1A", "label": "p21", "authors_fold_change": 1.8071, "authors_adjusted_p": 0.0002923, "ours_cpm_fold_change": 2.2053, "ours_directional_donors_up": 6, "ours_directional_donors_down": 0 }, { "gene": "CDKN2A", "label": "p16", "authors_fold_change": 0.2379, "authors_adjusted_p": 9.687e-7, "ours_cpm_fold_change": 0.4859, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "SERPINE1", "label": "PAI-1", "authors_fold_change": 0.4661, "authors_adjusted_p": 0.0002883, "ours_cpm_fold_change": 0.5503, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "IL1R1", "label": "IL1R1", "authors_fold_change": 0.5562, "authors_adjusted_p": 0.000062, "ours_cpm_fold_change": 0.657, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "MYC", "label": "MYC", "authors_fold_change": 0.6469, "authors_adjusted_p": 0.0034618, "ours_cpm_fold_change": 0.837, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "COL3A1", "label": "COL3A1", "authors_fold_change": 0.3383, "authors_adjusted_p": 0.00000304, "ours_cpm_fold_change": 0.3691, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "COL1A1", "label": "COL1A1", "authors_fold_change": 0.4217, "authors_adjusted_p": 0.06104, "ours_cpm_fold_change": 0.5087, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 }, { "gene": "IL1B", "label": "IL1B", "authors_fold_change": 0.9392, "authors_adjusted_p": 0.8451, "ours_cpm_fold_change": 1.0085, "ours_directional_donors_up": 2, "ours_directional_donors_down": 4 }, { "gene": "IL6", "label": "IL6", "authors_fold_change": 0.6373, "authors_adjusted_p": 0.1334, "ours_cpm_fold_change": 0.766, "ours_directional_donors_up": 2, "ours_directional_donors_down": 4 }, { "gene": "SRSF1", "label": "gene-level RNA; not protein", "authors_fold_change": 0.07109, "authors_adjusted_p": 5.455e-56, "ours_cpm_fold_change": 0.07168, "ours_directional_donors_up": 0, "ours_directional_donors_down": 6 } ], "interpretation": "Mixed expression signature. CXCL8 and CDKN1A rise in this induction condition while several aging-associated markers decline. This motivates a dose-, time- and tissue-specific safety-window hypothesis; it does not establish senescence, harm, cancer, protein activity or human benefit.", "safety_context": [ "SRSF1 gene-level RNA decrease cannot be interpreted as lower total SRSF1 protein because negative autoregulatory splicing can suppress endogenous transcript output.", "A separate experimental study reports SRSF1-promoted pancreatitis and KRASG12D-driven pancreatic cancer in a specific context; this is not evidence of identical risk in all tissues." ], "limitations": [ "Same originating study dataset; no independent biological replication.", "Six donor-derived fibroblast lines, one dose and one 3-day condition.", "Targeted panel and exploratory sign test without multiple-testing correction.", "No full transcriptome/isoform, protein, secreted cytokine, functional senescence, tumor or clinical analysis.", "The study's small animal groups and secondary human-cell analysis limit generalization." ], "artifacts": { "public_summary": "https://darkoza.com/science/reports/srsf1-aging-safety-window/public_summary.json", "public_deseq2_crosscheck": "https://darkoza.com/science/reports/srsf1-aging-safety-window/public_deseq2_crosscheck.json", "mapping_qc": "https://darkoza.com/science/reports/srsf1-aging-safety-window/mapping_qc_public.json", "reanalysis_source": "https://darkoza.com/science/reports/srsf1-aging-safety-window/reanalyze_public.py", "crosscheck_source": "https://darkoza.com/science/reports/srsf1-aging-safety-window/crosscheck_public_deseq2.py", "crosswalk_source": "https://darkoza.com/science/reports/srsf1-aging-safety-window/validate_geo_crosswalk.py" }, "references": [ "https://doi.org/10.1038/s43587-026-01234-8", "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325735", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10330071/", "https://pubmed.ncbi.nlm.nih.gov/20139984/", "https://doi.org/10.1016/j.celrep.2022.110985" ] }