Cited by 896Hematopoietic Stem Cell TransplantationAutophagy in Disease and TherapyMesenchymal stem cell research

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Autophagy maintains the metabolism and function of young and old stem cells

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Ho, Theodore T., Warr, Matthew R., Adelman, Emmalee R., Lansinger, Olivia M., Flach, Johanna, Verovskaya, Evgenia V., Figueroa, Maria E., Passegué, Emmanuelle·2017·Nature

DOI 10.1038/nature21388PMC PMC5344718

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Abstract

With age, haematopoietic stem cells lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress. Here we show that loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs haematopoietic stem-cell self-renewal activity and regenerative potential. Strikingly, most haematopoietic stem cells in aged mice share these altered metabolic and functional features. However, approximately one-third of aged haematopoietic stem cells exhibit high autophagy levels and maintain a low metabolic state with robust long-term regeneration potential similar to healthy young haematopoietic stem cells. Our results demonstrate that autophagy actively suppresses haematopoietic stem-cell metabolism by clearing active, healthy mitochondria to maintain quiescence and stemness, and becomes increasingly necessary with age to preserve the regenerative capacity of old haematopoietic stem cells.

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Authors: Ho, T. T., Warr, M. R., Adelman, E. R., Lansinger, O. M., Flach, J., Verovskaya, E. V., Figueroa, M. E., & Passegué, E.
Affiliations: University of California, San Francisco (US)
University of Michigan (US)
ORCID: Ho, Theodore T.
Warr, Matthew R.
Adelman, Emmalee R.
Lansinger, Olivia M.
Flach, Johanna
Verovskaya, Evgenia V.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-03
Volume: 543
Issue: 7644
Pages: 205-210
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature21388
PMC: PMC5344718
OpenAlex: W2592615787
Cited by: 896
References: 42
Citations by year: 2026: 58 · 2025: 67 · 2024: 95 · 2023: 103 · 2022: 107 · 2021: 124 · 2020: 118 · 2019: 93 · 2018: 90 · 2017: 40
FWCI: 71.87
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institute on Aging (T32AG000114)
National Heart, Lung, and Blood Institute (R01HL126947)
National Cancer Institute (R01CA184014)
National Institute of General Medical Sciences (T32GM008284)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: autophagy, hematopoietic stem cells, cellular aging, stem cell self-renewal, mitochondrial accumulation, myeloid differentiation, epigenetic regulation, metabolic stress, regenerative capacity, stem cell quiescence
MeSH terms: Cell Self Renewal, Animals, Autophagy, Female, Hematopoiesis, Hematopoietic Stem Cells, Male, Mitochondria, Cellular Senescence, Myeloid Cells, Epigenesis, Genetic, Mice

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Autophagy maintains the metabolism and function of young and old stem cells

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