Moderate Calorie Restriction Rewires Metabolism, Immunity for Longer Health Span

Caloric restriction improves metabolic and immune responses that help determine how long a person lives and how many years of good health they enjoy, a new study shows.

“Two years of modest calorie restriction reprogrammed pathways in fat cells that help regulate how mitochondria generate energy, the body’s anti-inflammatory responses, and potential longevity,” said Eric Ravussin, Ph.D., Associate Chief Executive Officer of Clinical Sciences at Pennington Biomedical Research Center. “In other words, calorie restriction modifies many of the metabolic and immune responses that increase life expectancy and health.”

The new study used data collected by Pennington Biomedical’s CALERIE 2 (Comprehensive Evaluation of the Long-Term Effects of Reducing Energy Intake), the longest-running trial of calorie restriction in humans. The new study is published in the journal Sciences.

The study found that people who reduced their calorie intake by about 14 percent over two years generated more T cells, which play a key role in immune function and slow the aging process.

Eric Ravussin, PhD, Associate Executive Director for Clinical Sciences at the Pennington Biomedical Research Center. Credit: Pennington Biomedical Research Center

“As people age, their thymuses shrink and produce fewer T cells. As a result, older people have a harder time fighting infections and certain types of cancer,” said Eric Ravussin, Ph.D., Associate Executive Director of Clinical Sciences at the Pennington Biomedical Research Center. “Calorie restriction helps keep the thymus from shrinking so the person makes more T cells.”

In addition to improving immunity, an increase in T cells is associated with a better ability to burn fatty acid stores for energy, Dr. Ravussin said. That’s important because if a person doesn’t burn this fuel, fat can accumulate in organs like muscles and the liver, leading to insulin resistance, obesity, type 2 diabetes, and aging.

The study had another important finding: a potential treatment to reduce age-related inflammation and improve metabolic health.

Studies have shown that restricting calories by 40 percent in rodents prolongs their lives. But there were tradeoffs in growth, reproduction, and immunity.

However, calorie restriction also reduces levels of the gene that encodes platelet-activating factor acetyl hydrolase (PLA2G7). The reduction of PLA2G7 produces health benefits that include the reduction of age-related inflammation and the improvement of metabolic health.

“If researchers can find a way to harness PLA2G7, they could create a treatment to extend a person’s period of health, the length of time a person experiences good health,” said Pennington Biomedical CEO John Kirwan, Ph. d

Reference: “Calorie Restriction Has a New Player” by Timothy W. Rhoads and Rozalyn M. Anderson, Feb 10, 2022, Sciences.
DOI: 10.1126/science.abn6576

This research was supported in part by the National Institutes of Health under awards AG031797, AG045712, P01AG051459, and AR070811 to VDD); the Glenn Foundation for Medical Research (VDD); Cure[{” attribute=””>Alzheimer’s Fund (V.D.D.); and the Aging Biology Foundation (M.N.A.). The CALERIE study was funded by the National Institute on Aging under awards U01AG022132, U01AG020478, U01AG020487, and U01AG020480. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the Pennington Biomedical Research Center

The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. The Center architected the “Obecity, USA” awareness and advocacy campaign to help solve the obesity epidemic by 2040. The Center conducts basic, clinical, and population research, and is affiliated with Louisiana State University. The research enterprise at Pennington Biomedical includes over 480 employees within a network of 40 clinics and research laboratories, and 13 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians, and other support personnel. Pennington Biomedical is located in state-of-the-art research facilities on a 222-acre campus in Baton Rouge, Louisiana.