Systemic signals regulate ageing and rejuvenation of blood stem cell niches

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. New blood for old Indirect evidence suggests that the declining function of haematopoietic stem and progenitor cells during ageing is influenced by signals from the microenvironment or stem cell niche, but experimental evidence in support of this hypothesis has been lacking. Now a study in mice confirms that age-associated changes in stem cell supportive niche cells do cause haematopoietic stem cell dysfunction. The age-dependent defects in niche cells are systemically regulated and are reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1 in the marrow microenvironment. Thus blood-borne factors in aged animals act via local niche cells to induce age-dependent disruption of stem cell. This suggests that targeting the circulatory environment to maintain function of niche cells and stem cells may extend the youthful function of the ageing blood system. Age-associated changes in stem cell supportive niche cells are shown to deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young