Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging
Open accessAbstract
-dependent deacetylase, is required for HSC maintenance and regenerative capacity at an old age by repressing the activation of the NLRP3 inflammasome in HSCs cell autonomously. With age, reduced SIRT2 expression and increased mitochondrial stress lead to aberrant activation of the NLRP3 inflammasome in HSCs. SIRT2 overexpression, NLRP3 inactivation, or caspase 1 inactivation improves the maintenance and regenerative capacity of aged HSCs. These results suggest that mitochondrial stress-initiated aberrant activation of the NLRP3 inflammasome is a reversible driver of the functional decline of HSC aging and highlight the importance of inflammatory signaling in regulating HSC aging.
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SIRT2 is necessary to prevent ageing in HSCs and can inhibit the inflammation (inflammasome) response that occurs in old HSCs.
“SIRT2, another member of the sirtuin family, is necessary to prevent ageing in HSCs, and can inhibit the inflammation (inflammasome) response that occurs in old HSCs119.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [119]
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References 61 · Cited by 161
- Authors
- Luo, H., Mu, W.-C., Karki, R., Chiang, H.-H., Mohrin, M., Shin, J. J., Ohkubo, R., Ito, K., Kanneganti, T.-D., & Chen, D.
- Affiliations
- University of California, Berkeley (US)
- St. Jude Children's Research Hospital (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Chen, Danica
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 26
- Issue
- 4
- Pages
- 945-954.e4
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6371804
- OpenAlex
- W2913021614
- Cited by
- 161
- References
- 61
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 17 · 2023: 23 · 2022: 20 · 2021: 26 · 2020: 17 · 2019: 8
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- ETH Zürich Research Collection
- Funders
- NIH (R01 DK101885, R01 DK117481, AG063404, T32 AG000266)
- National Institute of Food and Agriculture
- PackerWentz Endowment
- Chau Hoi Shuen Foundation (AI124346, AI101935, DK98263, DK115577)
- Leukemia and Lymphoma Society
- Glenn/AFAR Scholarship
- Dr. and Mrs. James C.Y. Soong Fellowship
- Government Scholarship for Study Abroad (GSSA) from Taiwan
- NSF
- Siebel Stem Cell Institute
- ITO Scholarship
- Honjo International Scholarship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- hematopoietic stem cell aging, NLRP3 inflammasome, mitochondrial stress, SIRT2, caspase-1, inflammation, stem cell maintenance, regenerative capacity, aging
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Hematopoietic Stem Cells, Mitochondria, Stress, Physiological, Cellular Senescence, Mice, Knockout, Mice, Sirtuin 2, Inflammasomes
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