Reducing overall calorie intake, without depriving the body of essential nutrients, may strengthen muscle and activate biological pathways and genes associated with healthy aging, a study conducted by National Institutes of Health (NIH) researchers found.
 
The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study, appearing in Aging Cell, examined whether moderate calorie restriction could achieve benefits in humans similar to those seen in animal studies. Over a two-year span, the goal for participants was to reduce caloric intake by 25%, but the highest the group was able to achieve was 12%. This relatively modest reduction was enough to activate most of the previously-identified biological pathways associated with healthy aging.
 
The authors sought to compare the group to previous calorie restriction studies. One study showed that individuals on calorie restriction lost muscle mass and an average of 20 pounds over the first year, and maintained their weight in the second year of the study. Despite losing muscle mass, the participants didn’t lose muscle strength, indicating calorie restriction improved the force generated by each unit of muscle mass, called muscle specific force.
 
In the present study, scientists used thigh muscle biopsies from the participants at baseline, and again at one-year and two-year follow-ups. They isolated mRNA, a molecule which contains code for muscle proteins, from the samples. The team determined the protein sequence of each mRNA and used the information to identify which genes originated specific mRNAs.
 
Analysis helped the scientists establish which genes during calorie restriction were upregulated, and which were downregulated. Calorie restriction activated many of the same gene pathways in humans as in mice and non-human primates, as told by previous research. Many of the upregulated genes were responsible for energy generation and metabolism, while downregulated inflammatory genes resulted in lower inflammation.
 
“Since inflammation and aging are strongly coupled, calorie restriction represents a powerful approach to preventing the pro-inflammatory state that is developed by many older people,” said Luigi Ferrucci, MD, PhD, corresponding author and scientific director of the National Institute of Aging.