New insight into the causes, consequences, and correction of hematopoietic stem cell aging

• Published in: Experimental hematology Vol. 125-126; pp. 1 - 5
• Main Authors: Mansell, Els, Lin, Dawn S., Loughran, Stephen J., Milsom, Michael D., Trowbridge, Jennifer J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-09-2023
• Subjects: Aged; Aging - pathology; Basic Medicine; Cell and Molecular Biology; Cell- och molekylärbiologi; Cellular Senescence - genetics; Hematologic Diseases - metabolism; Hematopoietic Stem Cells - metabolism; Humans; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2023.07.002

•Low-grade inflammation in early to mid-life accelerates mouse hematopoietic aging•The decline of niche factor insulin-like growth factor 1 drives the onset of hematopoietic aging•Middle age provides a window of opportunity for interventional strategies
Aging of hematopoietic stem cells (HSCs) is characterized by lineage bias, increased clonal expansion, and functional decrease. At the molecular level, aged HSCs typically display metabolic dysregulation, upregulation of inflammatory pathways, and downregulation of DNA repair pathways. Cellular aging of HSCs, driven by cell-intrinsic and cell-extrinsic factors, causes a predisposition to anemia, adaptive immune compromise, myelodys, plasia, and malignancy. Most hematologic diseases are strongly associated with age. But what is the biological foundation for decreased fitness with age? And are there therapeutic windows to resolve age-related hematopoietic decline? These questions were the focus of the International Society for Experimental Hematology (ISEH) New Investigator Committee Fall 2022 Webinar. This review touches on the latest insights from two leading laboratories into inflammatory- and niche-driven stem cell aging and includes speculation on strategies to prevent or correct age-related decline in HSC function.