A Discussion of Hematopoietic Stem Cell Aging

The aging of hematopoietic stem cells is an important contributing factor in the decline of the immune system in later life, resulting in reduced clearance of senescent cells and pathogens, alongside increasing chronic inflammation. One of the problems deriving from impaired hematopoiesis is that the production of immune cells becomes skewed towards myeloid lineages, biasing the immune system towards the above mentioned declines. There are a range of potential approaches that might help with these issues, from introducing new hematopoietic stem cells to suppressing chronic inflammation to small molecules that may favorably adjust the behavior of native cells. Age-related dysfunction of hematopoiesis isn't a simple challenge, however, as stem cell function depends on the supporting cells of the stem cell niche and the systemic signaling environment, rather than only on the integrity of the stem cell population itself.

There is a hot topic in stem cell research to investigate the process of hematopoietic stem cell (HSC) aging characterized by decreased self-renewal ability, myeloid-biased differentiation, impaired homing, and other abnormalities related to hematopoietic repair function. It is of crucial importance that HSCs preserve self-renewal and differentiation ability to maintain hematopoiesis under homeostatic states over time. Although HSC numbers increase with age in both mice and humans, this cannot compensate for functional defects of aged HSCs.

The underlying mechanisms regarding HSC aging have been studied from various perspectives, but the exact molecular events remain unclear. Several cell-intrinsic and cell-extrinsic factors contribute to HSC aging including DNA damage responses, reactive oxygen species (ROS), altered epigenetic profiling, polarity, metabolic alterations, impaired autophagy, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, nuclear factor- (NF-) κB pathway, mTOR pathway, transforming growth factor-beta (TGF-β) pathway, and wingless-related integration site (Wnt) pathway.

To determine how deficient HSCs develop during aging, we provide an overview of different hallmarks, age-related signaling pathways, and epigenetic modifications in young and aged HSCs. Knowing how such changes occur and progress will help researchers to develop medications and promote the quality of life for the elderly and possibly alleviate age-associated hematopoietic disorders. The present review is aimed at discussing the latest advancements of HSC aging and the role of HSC-intrinsic factors and related events of a bone marrow niche during HSC aging.

Link: https://doi.org/10.1155/2022/2713483


multiple cycles of water only fasting (48-120 hours) reverse age-dependent myeloid-bias, kill older and damaged immune cells and generate new ones. This happens even with an aged(or damaged)immune system and so must rejuvenate the stem cell niche also?

Posted by: erasmus at April 21st, 2022 6:04 AM

@Reason - what do you think of this research profiled today?:


"Blood stem cells are able to reproduce unlimited copies and differentiate into every type of human blood cell. Researchers have attempted to create blood stem cells in the lab from human pluripotent stem cells without success.

"Nobody has succeeded in making functional blood stem cells from human pluripotent stem cells because we didn't know enough about the cell we were trying to generate," Mikkola said in a news release.

The research team, which included scientists from Germany's University of Tübingen and Australia's Murdoch Children's Research Institute, used single-cell RNA sequencing and spatial transcriptomics to create the map. The technology allowed for the identification of unique genetic networks and functions of individual cells and detection of location within the embryo.

"We now have a manual of how hematopoietic stem cells are made in the embryo and how they acquire the unique properties that make them useful for patients," said UCLA scientist Vincenzo Calvanese, a co-author of the research and group leader at University College London. "

Posted by: jimofoz at April 22nd, 2022 4:20 PM
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