Aged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions
Open accessAbstract
While young blood can restore many aged tissues, its effects on the aged blood system itself and old hematopoietic stem cells (HSCs) have not been determined. Here, we used transplantation, parabiosis, plasma transfer, exercise, calorie restriction, and aging mutant mice to understand the effects of age-regulated systemic factors on HSCs and their bone marrow (BM) niche. We found that neither exposure to young blood, nor long-term residence in young niches after parabiont separation, nor direct heterochronic transplantation had any observable rejuvenating effects on old HSCs. Likewise, exercise and calorie restriction did not improve old HSC function, nor old BM niches. Conversely, young HSCs were not affected by systemic pro-aging conditions, and HSC function was not impacted by mutations influencing organismal aging in established long-lived or progeroid genetic models. Therefore, the blood system that carries factors with either rejuvenating or pro-aging properties for many other tissues is itself refractory to those factors.
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Old haematopoietic stem cells (HSCs) seem resistant to the effect of exercise.
“However, old HSCs seem to be resistant to the effect of exercise201, although the HSC niche and lymphoid progenitors can respond positively to exercise81.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [201]
Old HSCs appear resistant to the beneficial effect of dietary restriction.
“Old HSCs appear to be resistant to the beneficial effect of dietary restriction 201.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [201]
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Kobayashi, H., Watanuki, S., Shiozawa, Y., Oshima, M., Koide, S., Takayama, N., Morikawa, T., Haraguchi, M., Tamaki, S., Asakura, T., et al. (2026) · Science Advances · doi:10.1126/sciadv.aeb1346 · Cited by 1 · see citing works
- Authors
- Ho, T. T., Dellorusso, P. V., Verovskaya, E. V., Bakker, S. T., Flach, J., Smith, L. K., Ventura, P. B., Lansinger, O. M., Hérault, A., Zhang, S. Y., Kang, Y.-A., Mitchell, C. A., Villeda, S. A., & Passegué, E.
- Affiliations
- University of California, San Francisco (US)
- Columbia University Irving Medical Center (US)
- The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Hematology/Oncology Division, University of California, San Francisco, San Francisco, CA 1
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2021-05-25
- Volume
- 218
- Issue
- 7
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC8155813
- OpenAlex
- W3165498186
- Cited by
- 101
- References
- 80
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 22 · 2023: 21 · 2022: 17 · 2021: 6
- FWCI
- 10.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Hillblom Center for the Biology of Aging
- National Institutes of Health (F31HL151140, R35HL135763)
- The Netherlands Organization for Scientific Research
- BD Biosciences
- NYSTEM
- California Institute for Regenerative Medicine
- NIA (R01AG055797)
- Program for Breakthrough Biomedical Research
- Glenn Foundation for Medical Research
- Samuel Waxman Cancer Research Foundation
- 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
- hematopoietic stem cells, aging, young blood, parabiosis, plasma transfer, bone marrow microenvironment, caloric restriction, physical activity
- MeSH terms
- Aging, Animals, Bone Marrow, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mutation, Rejuvenation, Mice, SCID, Mice, Inbred NOD, Mice
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