Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging
- 16 September 2011
- journal article
- Published by Wiley in Journal of Anatomy
- Vol. 219 (5), 574-581
- https://doi.org/10.1111/j.1469-7580.2011.01423.x
Abstract
Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells.Keywords
This publication has 30 references indexed in Scilit:
- Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokinesMechanisms of Ageing and Development, 2010
- Aging Is Not Associated With Bone Marrow-Resident Progenitor Cell DepletionThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2010
- Mechanisms of Vascular Aging: New PerspectivesThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2010
- Age-related changes in total and regional fat distributionAgeing Research Reviews, 2009
- Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironmentNature, 2009
- The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs) to mechanical strain is inversely related to body mass index of the donorActa Orthopaedica, 2009
- Aging Reduces Skeletal Blood Flow, Endothelium-Dependent Vasodilation, and NO Bioavailability in RatsJournal of Bone and Mineral Research, 2007
- Anemia in the Elderly: A Public Health Crisis in HematologyHematology, 2005
- Aging and HaemopoiesisDrugs & Aging, 1996
- Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.The Journal of Experimental Medicine, 1996