Evidence for Hematopoietic Progenitor Cells to Buffer the Aging of Hematopoietic Stem Cells
Hematopoietic cell populations reside in the bone marrow. A tree of ever more specialized progenitor cell populations descends from the root hematopoietic stem cell population, responsible for ultimately producing red blood cells and white blood cells. Hematopoietic stem cell populations are known to become damaged and dysfunction with age, and this is one of the contributions to immune system dysfunction in later life. It also produces effects such as platelets that are more prone to causing inappropriate clotting and thrombosis. Here, researchers provide evidence to suggest that the intermediate hematopoietic progenitor cell populations are much less impacted by aging than is the case for hematopoietic stem cells, and might be buffering the loss of stem cell function to allow for maintained hematopoietic function. It is a little early to understand what this might mean for approaches to therapy, and what the implications are for the importance of hematopoietic stem cell function in aging. It is certainly interesting, however.
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 (MPPFs) as a potential source of age resilience.
This unique finding was emphasized by unchanged transcriptomic, proliferation, and mitochondrial capacity of young and old MPPFs, revealing remarkable similarities upon aging. Considering that HSCs functionally decline with age, yet intermediate progenitors remain unperturbed and "age resilient", we posit that MPPFs may play an essential role in protecting downstream progenitors from inheriting age-related properties from HSCs. We propose three potential mechanisms for how MPPFs maintain hematopoietic integrity and homeostasis with age.