|Aging Cell. 2011 Jan 18. doi: 10.1111/j.1474-9726.2011.00675.x. [Epub ahead of print]|
Age-related changes in human hematopoietic stem/progenitor cells.
Kuranda K, Vargaftig J, de la Rochere P, Dosquet C, Charron D, Bardin F, Tonnelle C, Bonnet D, Goodhardt M.
INSERM UMRS 940, Paris, France Institut Universitaire d'Hématologie, Université Paris 7 Denis Diderot, Paris, France Haematopoietic Stem Cell Laboratory, Cancer Research UK London Research Institute, London, UK Département de Biothérapies, Hôpital Saint-Louis, AP-HP; Paris, France Institut Paoli-Calmettes, Centre de Thérapie Cellulaire et Génique, Marseille, France.
Adult stem cells are critical for maintaining cellular homeostasis throughout life, yet the effects of age on their regenerative capacity are poorly understood. All lymphoid and myeloid blood cell lineages are continuously generated from hematopoietic stem cells present in human bone marrow. With age, significant changes in the function and composition of mature blood cells are observed. In this study, we report that age-related changes also occur in the human hematopoietic stem cell compartment. We find that the proportion of multipotent CD34(+) CD38(-) cells increases in the bone marrow of elderly (>70 years) individuals. CD34(+) CD38(+) CD90(-) CD45RA(+/-) CD10(-) and CD34(+) CD33(+) myeloid progenitors persist at the same level in the bone marrow, while the frequency of early CD34(+) CD38(+) CD90(-) CD45RA(+) CD10(+) and committed CD34(+) CD19(+) B-lymphoid progenitors decreases with age. In contrast to mice models of aging, transplantation experiments with immunodeficient NOD/SCID/IL-2R? null (NSG) mice showed that the frequency of NSG repopulating cells does not change significantly with age, and there is a decrease in myeloid lineage reconstitution. An age-related decrease in the capacity of CD34(+) cells to generate myeloid cells was also seen in colony-forming assays in vitro. Thus, with increasing age, human hematopoietic stem/progenitor cells undergo quantitative changes as well as functional modifications.
(so maybe we need to include a macrophage agonist in old people's vitamins?.... viewed through the narrow window of a CD33 freak, after about half an hour of thought.... not worth even reading this. :-)