Abstaining from eating for periods of two to four days at a time not only helps to protect the immune system from damage, but also leads to cell regeneration, according to a groundbreaking new piece of research*.

Scientists at the University of Southern California (USC) in the US say this is the first time a natural intervention has been found to trigger stem cell-based self-renewal of an organ or system. And the findings could have major implications for healthy ageing.

As people age, their immune system declines, making them more susceptible to disease; being able to prevent or reverse this process could help prevent illness in this group. It could also potentially benefit those with autoimmune disorders, and cancer patients whose immune systems are weakened by chemotherapy.

Flipping the switch Over a course of six months, the scientists looked at the impact prolonged fasting cycles had on mice as well as patients undergoing chemotherapy. Both the mice and the people went without food for two- to four-day periods.

In both cases, not eating initially lowered the white blood cell counts – the cells that defend the body against disease – as the body started getting rid of old or damaged cells. “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,” explains lead study author Valter Longo, a professor of gerontology and biological sciences at USC.

Eventually, however, prolonged periods of fasting in mice then “flipped a regenerative switch” which kick-started the stem cells into producing brand new white blood cells. This essentially rebooted the whole immune system.

The PKA enzyme
Importantly, the scientists also found that, when people don’t eat for long periods, levels of the enzyme PKA are lowered in the body. In previous studies, PKA has been linked to the regulation of stem cell self-renewal and the potential for one cell to develop into many different cell types.

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode,” clarifies Longo, who’s also the director of USC’s Longevity Institute.

“It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system. And 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 ageing, fasting cycles can generate, literally, a new immune system.”

Additional benefits
Other results from the study, which was published in the Cell Stem Cell journal in June, showed that long periods of fasting lowered levels of IGF-1, a growth hormone that’s associated with ageing, tumour progression and cancer risk.

In another pilot clinical trial on a small group of chemotherapy patients, Longo discovered that fasting for a 72-hour period before treatment protected the body against toxicity.

* Longo, V et al. Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeration and Reverse Immunosuppression, Cell Stem Cell, June 2014