Systemic signals regulate ageing and rejuvenation of blood stem cell niches

Department of Stem Cell and Regenerative Biology, Harvard University, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 42.35). 10/2010; 467(7317):872. DOI: 10.1038/nature09474
Source: PubMed

ABSTRACT Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.

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    • "This improvement diminished when cells from either young or old mice were cultured on an environment reconstituted from MSCs from old animals [16]. In addition, the aged phenotype of adult stem cells such as hematopoietic stem cells was reversed by exposing them to a young stem cell environment [29]. The precise mechanism of the interaction of stem cells with their local environment is largely unknown. "
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    • "As a systemic milieu [15], serum has an important influence on stem cell function [16]. Recent studies have suggested that old mouse serum induces the aging or dysfunction of satellite cells, embryonic stem cells, and hemopoietic stem cells [11], [13], [14]. However, the critical factors that promote stem cell aging in the serum of older individuals are still unclear. "
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