The role of stem cells in aging Gary Van Zant, Ying Liang  Experimental Hematology  Volume 31, Issue 8, Pages 659-672 (August 2003) DOI: 10.1016/S0301-472X(03)00088-2

Figure 1 Diminished functional capacity of hematopoietic stem cells during aging. A young stem cell population is characterized by few apoptotic cells, a mix of quiescent and active cells, the latter with robust self-renewal and differentiation capacity. Young stem cells show balanced differentiation into lymphoid and myeloid lineages (a). It is hypothesized that an aged stem cell population has a higher rate of apoptosis due to acquired cellular damage. There are fewer quiescent cells in the stem cell reserve and the active stem cells have restricted lineage potential (b). When an old stem cell population comes under hematopoietic stress, it is proposed that the rate of apoptosis increases as quiescent cells unsuccessfully make the activation step, further depleting the quiescent reserves. Active stem cells not only are hampered by lineage restrictions, but the number of differentiated progeny each produces is diminished, leading to a slow and blunted recovery (c). Experimental Hematology 2003 31, 659-672DOI: (10.1016/S0301-472X(03)00088-2)

Figure 2 Restriction in developmental potency of stem cells during aging. Cells of the inner cell mass of mammalian embryos have complete developmental potential (totipotency), through embryogenesis, to produce a viable and complete organism (a human in this example). Embryonic stem cell (ESC) lines derived from the inner cell mass retain totipotency and can be maintained in culture (a). Hematopoietic stem cells (HSC) in the bone marrow of young adults have a balanced mutlipotency to produce lymphoid (L) and myeloid (M) progeny in adequate numbers to fight infection, carry oxygen, and clot blood. Under certain experimental, and possibly physiological, conditions, stem cells in young bone marrow have expanded developmental potential to produce, for example, hepatocytes, muscle cells, endothelium, and neurons. Under no circumstances do these stem cells retain the potency to produce a new individual (b). In a continuum of restriction in developmental potential, stem cells derived from the bone marrow of the old may lose plasticity. Moreover, differentiation in hematopoietic lineages is skewed toward myeloid differentiation, at the expense of lymphopoiesis (c). Experimental Hematology 2003 31, 659-672DOI: (10.1016/S0301-472X(03)00088-2)

Figure 3 Differential pattern of aging of stem cells in chimeric mice. In embryo-aggregated chimeras, cells in all tissues, including the hematopoietic stem cell population, are, in this example, a mixture of DBA/2 and C57BL/6 cells. In young chimeras, stem cells of both strains produce blood cells to establish a balanced chimerism (a). During two years of aging, the stem cells of the short-lived strain stop contributing to hematopoiesis and the blood is composed entirely of C57BL/6 cells (b). If the marrow is at this point transplanted (Xplant), the quiescent (not senescent) DBA/2 stem cells are reactivated and produce blood cells necessary for engraftment (c). Within a few months of transplant, however, DBA/2 stem cells again are completely quiescent (d). Increasing quiescence of stem cells during aging may lead to diminished hematopoietic response to a crisis. The dramatic and nonphysiological conditions associated with a bone marrow transplant are apparently sufficient to at least temporarily cause activation. Experimental Hematology 2003 31, 659-672DOI: (10.1016/S0301-472X(03)00088-2)