Prolonged Fasting Promotes Immune System Regeneration

A new study suggest that prolonged cycles of fasting trigger stem-cell based regeneration of immune cells and the clearing out of old, damaged cells.

Researchers at the University of Southern California (USC; Los Angeles, USA), the University of Palermo (Italy), and other institutions have succeeded in demonstrating in a mouse model that fasting for 2–4 days at a time reduces circulating insulin-like growth factor 1 (IGF-1) levels and protein kinase A (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.


The researchers also found that multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias, supporting previous data on the protection of lymphocytes from chemotoxicity in fasting. The pro-regenerative effects of fasting on stem cells were reinforced by deficiency in either IGF-1 or PKA, and blunted by exogenous IGF-1. Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of human patients fasted for a 72-hour period prior to chemotherapy. The study was published on June 5, 2014, in the journal Cell Stem Cell.

“Switching off the gene for PKA is the key step that triggers the stem cells to shift to regeneration; it gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system,” said corresponding author Prof. Valter Longo, PhD, director of the USC Longevity Institute. “The good news is that the body also rids itself of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. If you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

According to the authors, the study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

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University of Southern California
University of Palermo