Two USC Davis Studies Led by Valter Longo Snag Most-Read Spots in Cell Press Journals

Two studies led by Edna Jones Professor in Gerontology and Professor in Biological Science Valter Longo, director of the USC Longevity Institute, have been listed as the most-read articles in their respective Cell Press journals.

“Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression,” the article in Cell Stem Cell, highlighted how fasting cycles induced immune system regeneration and was published in June 2014.

The study provides the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, showing that cycles of prolonged fasting not only protect against immune system damage — a major side effect of chemotherapy — but also shift immune system stem cells from a dormant state to a state of self-renewal.

The findings have major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as people age. By outlining how prolonged fasting cycles — periods of no food for two to four days at a time over the course of six months — kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency — that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system,” explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune 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 aging, fasting cycles can generate, literally, a new immune system.”

The Cell Metabolism article, “Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population,” examined high-protein diets and their effects on cancer and mortality rates and was published in March 2014.

In the study, which tracked a large sample of adults for nearly two decades, Long and his team found that eating a diet rich in animal proteins during middle age makes you four times more likely to die of cancer than someone with a low-protein diet — a mortality risk factor comparable to smoking. Not only is excessive protein consumption linked to a dramatic rise in cancer mortality, but middle-aged people who eat lots of proteins from animal sources — including meat, milk and cheese — are also more susceptible to early death in general.

However, rather than look at adulthood as one monolithic phase of life, as other researchers have done, the latest study considers how biology changes as we age and how decisions in middle life may play out across the human life span.

In other words, what’s good for you at one age may be damaging at another. Protein controls the growth hormone IGF-I, which helps our bodies grow but has been linked to cancer susceptibility. Levels of IGF-I drop off dramatically after age 65, leading to potential frailty and muscle loss. The study shows that while high-protein intake during middle age is very harmful, it is protective for older adults: those over 65 who ate a moderate- or high-protein diet were less susceptible to disease.

“There’s a misconception that because we all eat, understanding nutrition is simple. But the question is not whether a certain diet allows you to do well for three days, but can it help you survive to be 100?” Longo said.