Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging: Fat, stem cells, cytokines and aging
Open accessAbstract
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.
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A frequent observation is the natural replacement of hematopoietic BM with adipose tissue in the elderly.
“A frequent observation is the natural replacement of hematopoietic BM with adipose tissue in the elderly.50”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [50]
Through differentiation into mature adipocytes, multipotent MSCs lose their capacity to produce hematopoiesis-supporting factors such as CXCL-12, IGF-1, and Kitl, and the concentration of these is inversely correlated with the amount of BM fat.
“Through differentiation into mature adipocytes, multipotent MSCs lose their capacity to produce hematopoiesis supporting factors such as CXCL-12, IGF-1, and Kitl.The concentration of these is inversely correlated with the amount of BM fat.50”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [50]
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- Authors
- Tuljapurkar, S. R., McGuire, T. R., Brusnahan, S. K., Jackson, J. D., Garvin, K. L., Kessinger, M. A., Lane, J. T., O’ Kane, B. J., & Sharp, J. G.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Sharp, John G.
- Venue
- Journal of Anatomy
- Publisher
- Wiley
- Published
- 2011-09-16
- Volume
- 219
- Issue
- 5
- Pages
- 574-581
- ISSN
- 0021-8782 (ISSN-L)
- PMC
- PMC3191309
- OpenAlex
- W1526860677
- Cited by
- 129
- References
- 30
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 15 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 2 · 2013: 11 · 2012: 4
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Anatomy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG024912, R01AG024912)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- bone marrow fat content, hematopoietic stem cells, side population cells, aging, insulin-like growth factor I, CXCL12, interleukin-6, marrow adiposity
- MeSH terms
- Adipose Tissue, Adult, Aged, Aged, 80 and over, Aging, Bone Marrow, Cadaver, Cell Count, Enzyme-Linked Immunosorbent Assay, Female, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Cytokines, Young Adult
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