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



Hind A. Alkhatabi*



Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia; *Corresponding author



Hind Ali Alkhatabi - Email: haalkhatabi@uj.edu.sa


Article Type

Research Article



Received February 1, 2024; Revised February 29, 2024; Accepted February 29, 2024, Published February 29, 2024



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 (GOs), 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, we identified potential drugs such as salermide, celestrol, cercosporin, dorsomorphin dihydrochloride, and LDN-193189 monohydrochloride that can reverse the aging-associated signatures in BM-HSCs from healthy elderly. 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 health span in the elderly.



Aging, hematopoietic stem cells, bone marrow, GREIN, BioJupies, RNA sequencing, gene ontologies, Next Generation Knowledge Discovery, L1000CDS2, drugs, natural products.



Alkhatabi et al. Bioinformation 20(2): 180-189 (2024)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.