Publication Date:
2010-01-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayack, Shane R -- Shadrach, Jennifer L -- Kim, Francis S -- Wagers, Amy J -- 1 DP2 OD004345-01/OD/NIH HHS/ -- DP2 OD004345/OD/NIH HHS/ -- P30 DK036836/DK/NIDDK NIH HHS/ -- P30DK036836/DK/NIDDK NIH HHS/ -- T32DK07260-29/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jan 28;463(7280):495-500. doi: 10.1038/nature08749.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110993" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/blood/*physiology
;
Animals
;
Blood Cells/cytology/*physiology
;
Bone Marrow/metabolism
;
Cell Count
;
Cells, Cultured
;
Hematopoiesis/physiology
;
Insulin-Like Growth Factor I/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Osteoblasts/cytology
;
Rejuvenation/*physiology
;
*Signal Transduction
;
Stem Cells/cytology/*physiology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
