In all species, from fruit flies to mice to monkeys, a single strategy reduces the risk of cancer, heart disease and diabetes. It staves off age-related neurodegeneration. It consistently prolongs life.

The secret: Eat less.

By this point it’s close to being an established law of life extenstion. But why does calorie restriction work?

A new study takes us closer to understanding this process.

The Most in-Depth Cellular Aging Study Ever

Scientists at the Salk Institute for Biological Studies in La Jolla, California, have been exploring the molecular mechanisms behind calorie restriction for many years. They want to know why it influences cellular aging in such a positive way.

In 2007 they identified a critical gene called PHA-4 that specifically links calorie restriction to longevity.

Four years later they discovered two enzymes, WWP-1 and UBC-18, that work together to help regulate lifespan.

Earlier this year, in conjunction with scientists at the Chinese Academy of Sciences, they published the most detailed report to date of all the changes that occur at a cellular level in both normal and calorie-restricted diets.

For their study, published in the journal Cell in March, they compared two groups of rats. One ate a normal diet, while the other was supplied with the same diet but with 30 percent fewer calories. Calorie restriction started at age 18 months and finished at 27 months.

The human equivalent would be from age 50 to 70.

At the start and finish of these periods, 168,703 cells were isolated from 40 cell types in both groups. The cell samples were taken from the brain, muscle, kidney, liver, skin, bone marrow, fat tissue and the aorta artery.

The scientists measured gene activity in each cell, as well as overall cell type composition.

A Potent Way to Reduce Inflammation

The scientists discovered that even at 27 months – quite old for these little rodents – gene activity and many of the cells and tissues of the calorie-restricted group resembled those of young ones.

Overall, 57 percent of the age-related changes in cell composition seen in the tissues of the control group were absent in the calorie-restricted rodents.

The restricted diet led to reduced inflammation, less immune overreaction, diminished markers of cellular senescence (aging), and delayed onset of age-related diseases.

One of the authors, Jing Qu, said, “The primary discovery in the current study is that the increase in the inflammatory response during aging could be systematically repressed by caloric restriction.”

This is an important finding, because inflammation is thought to play a critical role in age-related diseases. There’s even a name for it – inflammaging.

It’s well-established that inflammation is a major cause or effect of most of the so-called diseases of aging in humans: heart disease, diabetes, arthritis, and cancer.

Of the genetic changes seen in the rat study, one particular gene stood out called Ybx1. This was altered in 23 different cell types, and may turn out to be especially important in the aging process. The scientists are planning to study this gene in more detail.

Another of the authors, Concepcion Rodriguez Esteban, added:

“People say that ‘you are what you eat,’ and we’re finding that to be true in lots of ways. The state of your cells as you age clearly depends on your interactions with your environment, which includes what and how much you eat.”


  1. https://www.sciencedirect.com/science/article/pii/S0092867420301525?via%3Dihub
  2. https://www.salk.edu/news-release/eat-less-live-longer/