Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
Open accessAbstract
Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models.
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Aged MuSCs and HSCs have increased glucose use and higher levels of glycolysis.
“Aged MuSCs and HSCs have increased glucose use and higher levels of glycolysis121–123.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [123]
Glycolysis and mitochondrial function decline during ageing.
“Glycolysis and mitochondrial function also decline during ageing.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [123]
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References 82 · Cited by 101
- Authors
- Hennrich, M. L., Romanov, N., Horn, P., Jaeger, S., Eckstein, V., Steeples, V., Ye, F., Ding, X., Poisa-Beiro, L., Lai, M. C., Lang, B., Boultwood, J., Luft, T., Zaugg, J. B., Pellagatti, A., Bork, P., Aloy, P., Gavin, A.-C., & Ho, A. D.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Heidelberg University (DE)
- Institute for Research in Biomedicine (ES)
- University of Oxford (GB)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Gavin, Anne-Claude
- Ho, Anthony D.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-10-01
- Volume
- 9
- Issue
- 1
- Pages
- 4004-4004
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6167374
- OpenAlex
- W2892605399
- Cited by
- 101
- References
- 82
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 14 · 2023: 14 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 7 · 2018: 1
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- European Commission (306240)
- Blood Cancer UK (13042)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- aging, hematopoietic stem and progenitor cells, bone marrow microenvironment, Warburg effect, central carbon metabolism, myeloid differentiation, human bone marrow
- MeSH terms
- Adult, Aging, Bone Marrow Cells, Carbon, Female, Glycolysis, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Cellular Senescence, Proteome, Gene Expression Profiling, Adult Stem Cells, Stem Cell Niche, Young Adult
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