Moderate Calorie Restriction Rewires Metabolism, Immunity for Longer Health Span

Calorie restriction improves metabolic and immune responses that help determine both 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 the pathways in fat cells that help regulate the way mitochondria generate energy, the body’s anti-inflammatory responses, and potentially longevity,” said Eric Ravussin, Ph.D., Associate Executive Director for Clinical Science at Pennington Biomedical Research Center. “In other words, calorie restriction rewires many of the metabolic and immune responses that boost lifespan and health span.”

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

The study found that people who cut 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 Science at 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 off infections and certain cancers,” said Eric Ravussin, Ph.D., Associate Executive Director for Clinical Science at Pennington Biomedical Research Center. “Calorie restriction helps prevent the thymus from shrinking so the person generates more T cells.”

In addition to improving immunity, an increase in T cells is associated with an improved ability to burn stores of fatty acids for energy, Dr. Ravussin said. That’s important because if a person doesn’t burn this fuel, the fat may build up in organs such as the muscle and 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 extended their lives. But there were tradeoffs in growth, reproduction, and immunity.

However, calorie restriction also reduces the levels of gene encoding platelet activating factor acetyl hydrolase (PLA2G7). Reducing PLA2G7 produces health benefits that include lowering age-related inflammation and improving metabolic health.

“If researchers can find a way to harness PLA2G7, they could create a treatment to extend a person’s health span, the time an individual experiences good health,” said Pennington Biomedical Executive Director John Kirwan, Ph.D.

Reference: “Caloric restriction has a new player” by Timothy W. Rhoads and Rozalyn M. Anderson, 10 February 2022, Science.
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 V.D.D.); the Glenn Foundation for Medical Research (V.D.D.); Cure 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.

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Comments ( 7 )
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  • Frosted Flake

    Said backwards, are you guys talking about WHY some people seem to gain weight just walking past a donut shop? …metabolism stuck in the wrong gear?

  • Joe Grafer

    Correlation does not make causation. Most of these studies are wrong to assume it does. It could be other factors associated with people who moderate their food intake.

  • Chris G

    Except that they describe the causal mechanism, i.e. the plat

  • Michael Lynch

    Many observational studies do conflate correlation with causation, but that doesn’t seem to be the case with this one. They describe the causal mechanism, as the poster above notes. A well designed study can overcome those limitations

  • Jburns

    Anyone who reads this- your liver controls your stasis weight. Calorie restriction keep prompts your liver to make energy from stored adipose tissue. 14-21 days of caloric restriction to activate gluconeogenesis

  • Morgan L Smith

    By caloric restriction do you mean a general limit that is adhered to for years or a caloric deficit that is maintained for years?

  • Dave N Noble

    Does Resveratrol 500mg reduce PLA2G7 to simulate caloric restriction.