Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

Mario Giuseppe Mirisola, Laura Perin, Stefano Da Sacco, Min Wei, Ben S. Lam, Chia-Wei Cheng, Xiaoying Zhou, Gregor B. Adams, John J. Kopchick, Valter D. Longo, David I. Quinn, Gregor B. Adams, Tanya B. Dorff

Risultato della ricerca: Articlepeer review

208 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)810-823
Numero di pagine14
RivistaCell Stem Cell
Volume14
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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