image: During fasting the number of hematopoietic stem cells increases but the number of the normally much more abundant white blood cells decreases. In young or healthy mice undergoing multiple fasting/re-feeding cycles, the population of stem cells increases in size although the number of white blood cells remain normal. In mice treated with chemotherapy or in old mice, the cycles of fasting reverse the immunosuppression and immunosenescence, respectively. view more
Credit: <i>Cell Stem Cell</i>, Cheng et al.
While chemotherapy can save lives, it can also cause many side effects, including the depletion of immune cells. Also, even in the absence of chemotherapy, normal aging takes a heavy toll on the immune system, leading to immune deficiencies and a higher risk of developing leukemia and a variety of malignancies with age. Now researchers reporting in the June 5th issue of the Cell Press journal Cell Stem Cell have found that a simple dietary intervention—periodic fasting—may combat both chemotherapy-induced and aging-related changes in immune cell function by replenishing stem cells in the blood. The findings suggest that fasting may provide benefits for cancer patients, the elderly, and people with various immune defects.
It's estimated that more than one-fifth of cancer-related deaths are hastened, or even caused, by toxic effects of chemotherapy rather than the cancer itself. These toxicities can reduce the overall effectiveness of anticancer treatments by limiting the dosage and frequency of chemotherapeutic interventions that are tolerable to patients. Currently there are no interventions to lessen the side effects that chemotherapy has on the immune system or to prevent the immune cell dysfunction that occurs with aging.
Previous work by Dr. Valter Longo, of the University of Southern California, and his colleagues revealed that temporary nutrient restriction could increase stem cells' resistance to certain stressors. In their latest work, they tested whether fasting could have protective effects for immune cells such as white blood cells. "We show that prolonged fasting periods cause a major reduction in white blood cell number followed by its replenishment after refeeding," said Dr. Longo. "We discovered that this effect, which may have evolved to reduce energy expenditure during periods of starvation, is able to switch stem cells to a mode able to not only regenerate immune cells and reverse the immunosuppression caused by chemotherapy, but also rejuvenate the immune system of old mice." The researchers found that protection against white blood cell loss also occurred in human patients who fasted for a single 72-hour period prior to platinum-based chemotherapy as part of a phase 1 clinical trial.
With additional experiments, the investigators discovered that fasting provides its protective effects by reducing levels of insulin-like growth factor-1 (IGF-1), a protein with key roles in growth and aging. Therefore, fasting or treatments that target the IGF-1 pathway might provide similar benefits for cancer patients, the elderly, and people with immune defects. "We and others are currently testing the effect of fasting-mimicking diets on the protection of patients against chemotherapy's side effects, and we're also testing the role of multiple cycles of a fasting-mimicking diet on the immune system in generally healthy middle-aged and elderly subjects," said Dr. Longo.
Cell Stem Cell, Cheng et al.: "Prolonged Fasting reduces IGF-1/PKA to promote hematopoietic stem cell-based regeneration and reverse immunosuppression."
Journal
Cell Stem Cell