From Old to Young: Rejuvenating Effects of Fasting on the Immune System

By Roberta Attanasio

The beneficial effects of prolonged fasting — fasting that lasts 48–120 hours — have been known for several years. One of these effects is the enhancement of the cellular resistance to toxins in both experimental animals and humans. Now, results from a new study (Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression) published in the journal Cell Stem Cell (June 5, 2014), show that  cycles of prolonged fasting protect against damage to the immune system and induce its regeneration, shifting hematopoietic stem cells from an inactive state to a state of self-renewal.

Stem cells are cells that have the ability to divide and develop into many different cell types in the body during early life and growth. Stem cells may also help repair the body by dividing to replenish cells that are damaged by disease, injury, or normal wear. When a stem cell divides, each new cell has the potential either to remain a stem cell or to become another type of cell with a more specialized function, such as a nerve cell, a skin cell, or a red blood cell.

Hematopoietic stem cells form all red cells, the white cells of the immune system, and others. They are ultimately responsible for the constant renewal of blood — the production of billions of new red and white cells each day. The study shows that, during prolonged fasting, the number of hematopoietic stem cells increases, while the number of the normally much more abundant white blood cells — which are the immune cells — decreases. Such decrease occurs because older and damaged immune cells die. Eventually, the stem cells generate new, healthy white blood cells. In mice treated with chemotherapy (which results in immunosuppression) or in old mice, cycles of fasting reverse the immunosuppression and immunosenescence, respectively. Cycles of fasting consist of periods of no food for two to four days at a time over the course of six months.

During each cycle of fasting, the depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduces the enzyme PKA and also lowers the levels of IGF-1, a growth-factor hormone linked to aging, tumor progression and cancer risk.

Valter Longo, one of the researchers involved in the study, said in a press release “PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the ‘okay’ for stem cells to go ahead and begin proliferating and rebuild the entire system. The good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy. Tanya Dorff, another researcher involved in the study, said in the press release “While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy. More clinical studies are needed, and any such dietary intervention should be undertaken only under the guidance of a physician.”