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发表于 2015-4-2 08:40:59
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Saying No to Drugs: Fasting Protects Hematopoietic Stem Cells from Chemotherapy and Aging
Cell Stem Cell, Volume 14, Issue 6, 5 June 2014, Pages 704-705
Christopher Hine, James R. Mitchell
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Abstract
Aging and chemotherapeutics damage hematopoietic stem cells (HSCs), leading to dysregulation of asymmetric division and subsequent immunosuppression and blood-related diseases. In this issue, Cheng et al. (2014) use prolonged fasting as a medical intervention to decrease IGF-1/PKA signaling and protect HSCs against chemotherapeutic toxicity and promote rejuvenation.
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Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse ImmunosuppressionOriginal Research Article
Cell Stem Cell, Volume 14, Issue 6, 5 June 2014, Pages 810-823
Chia-Wei Cheng, Gregor B. Adams, Laura Perin, Min Wei, Xiaoying Zhou, Ben S. Lam, Stefano Da Sacco, Mario Mirisola, David I. Quinn, Tanya B. Dorff, John J. Kopchick, Valter D. Longo
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Summary
Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration. |
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