title: SIRT3 reverses aging-associated degeneration.
abstract: 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.
authors: Program in Metabolic Biology, Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Katharine
authors: K
authors: Brown
authors: Stephanie
authors: S
authors: Xie
authors: Xiaolei
authors: X
authors: Qiu
authors: Mary
authors: M
authors: Mohrin
authors: Jiyung
authors: J
authors: Shin
authors: Yufei
authors: Y
authors: Liu
authors: Dan
authors: D
authors: Zhang
authors: David T
authors: DT
authors: Scadden
authors: Danica
authors: D
authors: Chen
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D056566:Sirtuin 3
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