Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging
Open accessAbstract
Decline in hematopoietic stem cell (HSC) function with age underlies limited health span of our blood and immune systems. In order to preserve health into older age, it is necessary to understand the nature and timing of initiating events that cause HSC aging. By performing a cross-sectional study in mice, we discover that hallmarks of aging in HSCs and hematopoiesis begin to accumulate by middle age and that the bone marrow (BM) microenvironment at middle age induces and is indispensable for hematopoietic aging. Using unbiased approaches, we find that decreased levels of the longevity-associated molecule IGF1 in the local middle-aged BM microenvironment are a factor causing HSC aging. Direct stimulation of middle-aged HSCs with IGF1 rescues molecular and functional hallmarks of aging, including restored mitochondrial activity. Thus, although decline in IGF1 supports longevity, our work indicates that this also compromises HSC function and limits hematopoietic health span.
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Reduced levels of IGF1 in the bone marrow environment promote HSC ageing, and reduced production of IGF1 by stromal fibroblasts can impair skin stem cells during ageing.
“Reduced levels of IGF1 in the bone marrow environment (probably because of reduced production by old niche cells) also promote HSC ageing133, although low IGF1 levels lead to increased longevity at the organismal level. Reduced production of IGF1 by stromal fibroblasts can also impair skin stem cells during ageing134.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [133]
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Ageing and rejuvenation of tissue stem cells and their niches
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- Authors
- Young, K., Eudy, E., Bell, R., Loberg, M. A., Stearns, T., Sharma, D., Velten, L., Haas, S., Filippi, M.-D., & Trowbridge, J. J.
- Affiliations
- Jackson Laboratory (US)
- Cincinnati Children's Hospital Medical Center (US)
- Universitat Pompeu Fabra (ES)
- German Cancer Research Center (DE)
- Corresponding author
- Trowbridge, Jennifer J.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 28
- Issue
- 8
- Pages
- 1473-1482.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC8349778
- OpenAlex
- W3152911680
- Cited by
- 216
- References
- 59
- Citations by year
- 2026: 38 · 2025: 42 · 2024: 57 · 2023: 43 · 2022: 27 · 2021: 9
- FWCI
- 22.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Ellison Medical Foundation (T32HD007065)
- NCI (P30CA034196)
- American Society of Hematology (P30CA034196)
- NIDDK
- NIA
- Leukemia and Lymphoma Society
- European Molecular Biology Laboratory
- NICHD (T32HD007065)
- Ministerio de Ciencia e Innovación
- Generalitat de Catalunya
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoietic stem cell aging, insulin-like growth factor I, bone marrow microenvironment, middle age (human life stage), healthspan, mitochondrial activity, hallmarks of aging, hematopoiesis, longevity
- MeSH terms
- Aging, Animals, Bone Marrow, Cross-Sectional Studies, Hematopoiesis, Hematopoietic Stem Cells, Mice, Stem Cell Niche
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