SIRT3 Reverses Aging-Associated Degeneration
Open accessAbstract
Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.
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Ectopic induction of SIRT3 improves aged HSC function by enhancing SOD2 antioxidant activity.
“ectopic induction of SIRT3 expression improves the function of aged HSCs by enhancing the antioxidant activity of SOD2 (ref. 30).”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [30]
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- Authors
- Brown, K., Xie, S., Qiu, X., Mohrin, M., Shin, J., Liu, Y., Zhang, D., Scadden, D. T., & Chen, D.
- Affiliations
- University of California, Berkeley (US)
- Harvard University (US)
- Corresponding author
- Scadden, David T.
- Chen, Danica
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 3
- Issue
- 2
- Pages
- 319-327
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC3582834
- OpenAlex
- W2099348677
- Cited by
- 436
- References
- 27
- Citations by year
- 2026: 17 · 2025: 29 · 2024: 22 · 2023: 35 · 2022: 26 · 2021: 42 · 2020: 49 · 2019: 38 · 2018: 37 · 2017: 31 · 2016: 31 · 2015: 30 · 2014: 33 · 2013: 16
- FWCI
- 17.10
- 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)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Searle Scholars Program
- National Institute on Aging (R01AG040990)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- SIRT3, sirtuins, aging, hematopoietic stem cells, mitochondrial protein acetylation, mitochondrial homeostasis, oxidative stress, stem cell self-renewal, tissue regeneration, stress response
- MeSH terms
- Acetylation, Animals, Cells, Cultured, Hematopoietic Stem Cells, Mitochondria, Up-Regulation, Cellular Senescence, Reactive Oxygen Species, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Oxidative Stress, Mitochondrial Proteins, Mice, Sirtuin 3
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