in the bone marrow
New research indicates that cycles of prolonged fasting may prevent chemotherapy-induced immunosuppressive toxicity and induce regeneration of the hematopoietic system.
Long periods of fasting reduced damage in bone marrow stem and progenitor cells and protected both mice and humans from chemotoxicity.
In mice, the fasting cycles “flipped a regenerative switch,” changing the signaling pathways for hematopoietic stem cells (HSCs).
Researchers reported these results in Cell Stem Cell.
“We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system,” said study author Valter Longo, PhD, of the University of Southern California in Los Angeles.
“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged. What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then, when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?”
The researchers found that prolonged fasting reduced the enzyme PKA, which regulates HSC self-renewal and pluripotency.
“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode,” Dr Longo said. “It gives the ‘okay’ for stem cells to go ahead and begin proliferating and rebuild the entire system.”
Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that has been linked to aging, tumor progression, and cancer risk.
In addition to downregulating the IGF-1/PKA pathway in HSCs, prolonged fasting protected hematopoietic cells from chemotoxicity and promoted HSC self-renewal to reverse immunosuppression.
Experiments revealed that inhibiting IGF-1 or PKA signaling mimicked the effects of prolonged fasting.
The researchers also analyzed a small group of patients from a pilot study evaluating the effects of fasting before chemotherapy. Fasting for 72 hours, but not 24 hours, ensured that patients had normal lymphocyte counts and maintained a normal lineage balance in white blood cells after chemotherapy.
Dr Longo’s lab is now conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.
