Deciphering aging-associated molecular mechanisms in bone marrow derived hematopoietic stem cells in the elderly using NGS data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38497076", "kind": "science-record", "revision": 5, "content_hash": "sha256:4d6ebe89d411adb3aca6ba63d52f656e830478a6d067cfb6dba91f09cabc8f63", "created_at": "2026-11-01T19:20:26Z", "updated_at": "2026-11-01T22:53:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deciphering aging-associated molecular mechanisms in bone marrow derived hematopoietic stem cells in the elderly using NGS data.", "doi": "10.6026/973206300200180", "pmid": "38497076", "authors": ["Hind A Alkhatabi"], "journal": "Bioinformation", "year": 2024, "abstract": "Aging is a complex process that is not yet fully understood. Despite advancements in research, a deeper understanding of the underlying biological mechanisms is necessary to develop interventions that promote healthy longevity. The aim of this study was to elucidate the complex mechanisms associated with healthy aging and longevity in healthy elderly individuals. The RNA sequencing (RNA-seq) data used in this study was obtained from the Gene Expression Omnibus (GEO) database (accession number GSE104406), which was collected from Fluorescent Activated Cell Sorting (FACS) of human bone marrow derived human hematopoietic stem cells (BM-HSCs) (Lineage-, CD34+, CD38-) young (18-30 years old) and aged (65-75 years old) donors who had no known hematological malignancy, with 10 biological replicates per group. The GEO RNA-seq Experiments Interactive Navigator (GREIN) software was used to obtain raw gene-level counts and filtered metadata for this dataset. Next generation knowledge discovery (NGKD) tools provided by BioJupies were used to obtain differentially regulated pathways, gene ontologies (GO), and gene signatures in the BM-HSCs. Finally, the L1000 Characteristic Direction Signature Search Engine (L1000CDS2) tool was used to identify specific drugs that reverse aging-associated gene signatures in old but healthy individuals. The down-regulation of signaling pathways such as longevity regulation, proteasome, Notch, apoptosis, nuclear factor kappa B (NFkB), and peroxisome proliferator-activated receptors (PPAR) signaling pathways in the BM-HSCs of healthy elderly. GO functions related to negative regulation of bone morphogenetic protein (BMP), telomeric DNA binding, nucleoside binding, calcium -dependent protein binding, chromatin-DNA binding, SMAD binding, and demethylase activity were significantly downregulated in the BM-HSCs of the elderly compared to the healthy young group. Importantly, potential drugs such as salermide, celestrol, cercosporin, dorsomorphin dihydrochloride, and LDN-193189 monohydrochloride that can reverse the aging-associated signatures in HSCs from healthy elderly were identified. The analysis of RNA-seq data based on NGKD techniques revealed a plethora of differentially regulated pathways, gene ontologies, and drugs with anti-aging potential to promote healthspan in the elderly.", "claims": [{"id": "claim-method", "statement": "In order to detect differentially expressed genes (DEGs) between healthy young and healthy elderly persons, the raw counts were transformed into log10 counts per million (log CPM) using the limma R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38497076", "locator": "sections[5] \"BioJupies Analysis:\" paragraph 2", "quote": "In order to detect differentially expressed genes (DEGs) between healthy young and healthy elderly persons, the raw counts were transformed into log10 counts per million (log CPM) using the limma R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "RNA-seq data from the Gene Expression Omnibus (GEO) database (accession number GSE104406) was utilized in the present study. This data was collected from Fluorescent Activated Cell Sorting (FACS) isolated human bone marrow derived human HSCe (Lineage-, CD34+, CD38-) (BM-HSCs) young (18-30) and aged (65-75) donors who had no known hematological malignancy, with 10 biological replicates per group.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38497076", "locator": "sections[4] \"Data Source:\" paragraph 2", "quote": "RNA-seq data from the Gene Expression Omnibus (GEO) database (accession number GSE104406) was utilized in the present study. This data was collected from Fluorescent Activated Cell Sorting (FACS) isolated human bone marrow derived human HSCe (Lineage-, CD34+, CD38-) (BM-HSCs) young (18-30) and aged (65-75) donors who had no known hematological malignancy, with 10 biological replicates per group."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Analysis of GSE104406 identified 15,028 differentially expressed genes between healthy elderly and healthy young BM-HSCs and implicated downregulated aging-related pathways, gene ontologies, and candidate anti-aging drugs or natural products.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38497076", "locator": "sections[8] \"Results:\" paragraph 2", "quote": "Utilizing the filtered metadata and raw counts from GREIN, 15028 DEGs were identified between the two groups (aged, healthy vs. young, healthy as depicted in the volcano plot (Figure 1A derived from BioJupies analysis."}, {"asset": "source:pmid:38497076", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The analysis of RNA-seq data based on NGKD techniques revealed a plethora of differentially regulated pathways, gene ontologies, and drugs with anti-aging potential to promote healthspan in the elderly."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Analysis of GSE104406 identified 15,028 differentially expressed genes between healthy elderly and healthy young BM-HSCs and implicated downregulated aging-related pathways, gene ontologies, and candidate anti-aging drugs or natural products.", "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:38497076"], "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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