Results of a new study on mice and a phase 1 trial of humans
suggest that prolonged
cycles of fasting - for 2-4 days at a time - not only protect against
toxic effects of chemotherapy, but also trigger stem cell regeneration
of new immune cells
and clearing out of old, damaged cells.
The study, by researchers from the University of Southern California (USC) in Los Angeles, and published in the journal Cell Stem Cell, is the first to show that a natural intervention
can trigger regeneration of an organ or system through stem cells.
The team believes the findings could benefit people with immune system damage, for example if
they have received chemotherapy treatment for cancer. It could also benefit the elderly whose
immune systems are weakened through aging, making them more susceptible to disease.
The scientists say prolonged fasting appears to shift stem cells of the immune system from a
dormant state to an active state of self-renewal.
Results from experiments with mice and a phase 1 human clinical trial showed that long periods
of fasting significantly lowered levels of white blood cells. In the mice, it flipped a switch
that changed the signaling pathways of hematopoietic stem cells - a group of stem cells that
generate blood and immune systems.
"We could not predict that prolonged fasting would have such a remarkable effect in promoting
stem cell-based regeneration of the hematopoietic system," says Valter Longo, a professor of
Gerontology and the Biological Sciences at the USC Davis School of Gerontology, and director of the
USC Longevity Institute.
He says that when you stop eating, the body uses up stored glucose, fat and ketones, and also
recycles worn out and damaged immune cells.
"What we started noticing in both our human work and animal work is that the white blood cell
count goes down with prolonged fasting," he explains. "Then when you re-feed, the blood cells come
back. So we started thinking, well, where does it come from?"
In mice, prolonged fasting replenished worn out immune cells with new ones
The
researchers found that fasting for 2-4 days reduced PKA, an enzyme that
is involved in extending lifespan in simple organisms.
the course of 6 months, killed older and damaged immune cells and generated new ones.
During each fasting cycle, the drop in white cell levels triggered a stem-cell based
regeneration of new immune cells. In particular, prolonged fasting reduced PKA, an enzyme that the
team had previously discovered is involved in extending lifespan in simple organisms.
Other studies have also linked PKA to the control of stem cell self-renewal and pluripotency -
the extent to which they can become different cell-types.
Prolonged fasting also led to a drop in IGF-1, a growth factor hormone linked to aging, cancer
and tumor progression.
Switching off the gene for PKA is the key step that triggers the stem cells to shift to
regeneration, Prof. Longo says. "It gives the OK for stem cells to go ahead and begin
proliferating and rebuild the entire system."
And the good news, he adds, 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. Now, if you start with a
system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new
immune system."
Three-day fast protected cancer patients from toxic chemo effects
In a clinical trial involving a small group of cancer patients, the team also found thatfasting for 3 days before receiving chemotherapy protected them from its toxic effects.
While chemotherapy saves lives, it also causes significant damage to the immune system, and the
team hopes their findings show that fasting may help to minimize some of that harm.
Meanwhile, there is no suggestion that people should try to get these same effects by prolonged
fasting, which should only be done under medical supervision.
More clinical studies are now needed to test the effectiveness of the approach in humans and
also examine the side effects.
Prof. Longo says they are now investigating whether these same regeneration effects work with
other systems and organs as well as the immune system. His lab is already planning further animal
studies and clinical trials.
Funds from the National Institute of Aging of the National Institutes of Health (NIH), the V
Foundation and the National Cancer Institute of the NIH helped finance the study.
Meanwhile, Medical News Today recently reported how stem cells show potential for brain
damage repair. Research from Australia suggests by manipulating cell-surface proteins it may
be possible to get bone marrow stem cells to differentiate into brain cells. If the method proves
viable, it could lead to ways of generating new brain cell populations for repairing brain
damage.
Written by Catharine Paddock PhD
