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Stem cells and the aging hematopoietic system

Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA.
Current opinion in immunology (Impact Factor: 7.87). 08/2010; 22(4):500-6. DOI: 10.1016/j.coi.2010.06.007
Source: PubMed

ABSTRACT Advancing age is accompanied by a number of clinically significant conditions arising in the hematopoietic system that include: diminution and decreased competence of the adaptive immune system, elevated incidence of certain autoimmune diseases, increased hematological malignancies, and elevated incidence of age-associated anemia. As with most tissues, the aged hematopoietic system also exhibits a reduced capacity to regenerate and return to normal homeostasis after injury or stress. Evidence suggests age-dependent functional alterations within the hematopoietic stem cell compartment significantly contribute to many of these pathophysiologies. Recent developments have shed light on how aging of the hematopoietic stem cell compartment contributes to hematopoietic decline through diverse mechanisms.

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    • "Aged LNK ) ⁄ ) HSCs are far superior to aged WT HSCs in their abilities to repopulate both primary and secondary hosts. Additionally, aged WT HSCs displayed a lineage output profoundly skewed toward myelopoiesis , a phenomenon that has been attributed to the expansion of a specific subset of HSCs clones (Beerman et al., 2010), contrasting the balanced lineage program exhibited by aged LNK ) ⁄ ) HSCs (Fig. 2A, B). It remains to be seen whether knockdown of LNK in aged WT HSCs would lead to a similar repopulating potential upon transplantation as that of aged LNK ) ⁄ ) HSCs that have never 'seen' LNK throughout their ontogeny. "
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    • "In humans, only fragmentary and contradictory information is available concerning age-related changes in HSC (Waterstrat et al., 2008; Taraldsrud et al., 2009; Beerman et al., 2010). One study (Chatta et al., 1993) suggested that the proportion of HSC and in particular myeloid progenitors in mononucleated cells was the same in young and elderly adults but the generation of mixed granulocyte–macrophage colonies decreased with age (Marley et al., 1999). "
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