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: 7.48). 08/2010; 22(4):500-6. DOI: 10.1016/j.coi.2010.06.007
Source: PubMed


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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    • "The aged pool of HSC is often characterized by a marked shift in lymphoid and myeloid lineage output. Such age-associated myeloid skewing of the differentiation potential, together with decreased homing efficiency , contributes to changes in the cellular composition of the HSC compartment and is believed to be an important contributor to the decline of immune competence in the elderly (Beerman et al., 2010; Gui et al., 2007; Müller and Pawelec, 2014). Studies on telomerase knockout mice have demonstrated that telomere dysfunction and accumulation of DNA damage induces alterations in the stem-cell environment, leading in turn to HSCintrinsic deficiencies in aged mice (Ju et al., 2007; Song et al., 2012). "
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    Full-text · Article · Feb 2015 · Ageing Research Reviews
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    • "During normal haematopoiesis, the peripheral blood is estimated to have contributions from ~1000 HSCs (Catlin et al., 2011), whereas at any given time the majority of adult HSCs are in a quiescent state (Arai et al., 2004; Li and Clevers, 2010). On average, human HSCs are thought to divide once every 40 weeks (Catlin et al., 2011); however, blood cell production is a continuous process throughout life, with an adult human producing an estimated 1011 cells daily (Beerman et al., 2010). These properties make HSCs, like other tissue stem cells, prime targets for malignant transformation. "
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    • "Given that the thymus requires the continual input of bone marrow progenitors, any age-related alterations in hematopoietic stem cells (HSC) function could conceivably contribute toward thymic involution. Studies have demonstrated that aged HSC appear to exhibit an increased bias toward myeloid differentiation together with a reduced capacity toward lymphoid maturation; which has been observed in mice and human (31, 32). Such alterations in HSC function may manifest within early thymocyte progenitor (ETP) activity. "
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