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Publication : Aging of hematopoietic stem cells is inconsequential to progenitor cell function.

First Author  Myers J Year  2026
Journal  Stem Cell Reports Volume  21
Issue  7 Pages  102965
PubMed ID  42314672 Mgi Jnum  J:390460
Mgi Id  MGI:8394549 Doi  10.1016/j.stemcr.2026.102965
Citation  Myers J, et al. (2026) Aging of hematopoietic stem cells is inconsequential to progenitor cell function. Stem Cell Reports 21(7):102965
abstractText  Aging of the hematopoietic system has profound consequences for organismal health and longevity, attributed to the well-characterized functional aging of hematopoietic stem cells (HSCs). Here, we tested whether progenitor cells may demonstrate age resistance to enable hematopoietic homeostasis throughout life despite the functional decline of upstream HSCs. Strikingly, our results revealed unwavering reconstitution capacity by young and old progenitors, demonstrating that intermediate progenitors are functionally unaffected by aging and placing Flk2+ multipotent progenitors (MPP(F)s) as a potential source of age resilience. This unique finding was emphasized by unchanged transcriptomic, proliferation, and mitochondrial capacity of young and old MPP(F)s, revealing remarkable similarities upon aging. Considering that HSCs functionally decline with age, yet intermediate progenitors remain unperturbed and "age resilient", we posit that MPP(F)s may play an essential role in protecting downstream progenitors from inheriting age-related properties from HSCs. We propose three potential mechanisms for how MPP(F)s maintain hematopoietic integrity and homeostasis with age.
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