Investigating the biological mechanisms brought about by calorie restriction, a new study from researchers at the US National Institutes of Health (NIH) has found that a moderate reduction in calorie intake can improve muscle health and activate biological pathways important for good health.
Published in Aging Cell, this new study analyses biological mechanisms related to calorie restriction, to observe whether a similar positive health effect as seen in animals was replicated in humans.
Calorie restriction is essentially decreasing caloric intake without depriving the body of essential nutrients. In previous animal studies, caloric restriction has shown to positively affect skeletal muscle growth and also delay the progression of age-related diseases. However, until recently, information on the long-term effects of calorie restriction on humans has been sparse.
Analysing data collected from participants in the ‘Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy’ (CALERIE) study, the researchers found that, during a two-year period, while the goal was to reduce their daily caloric intake by 25%, the most participants were able to achieve was a reduction of 12%. Nonetheless, this moderate reduction was enough to activate most biological pathways associated with healthy ageing.
“A 12% reduction in calorie intake is very modest. This kind of small reduction in calorie intake is doable and may make a big difference in your health,” said Dr Luigi Ferrucci, scientific director at the National Institute of Aging (NIA) and co-author of the study.
The researchers then sought to understand the molecular underpinnings of the benefits seen in earlier limited research of calorie restriction in humans. One study showed that individuals on calorie restriction lost muscle mass and an average of 20 pounds of weight over the first year and maintained their weight for the second year. However, despite losing muscle mass, calorie restriction participants did not lose muscle strength, indicating calorie restriction improved the amount of force generated by each unit of muscle mass, called muscle-specific force.
For the new study, scientists used thigh muscle biopsies from CALERIE participants that were collected when individuals joined the study and at one-year and two-year follow-ups. They performed comprehensive RNA (ribonucleic acid) sequencing analysis on skeletal muscle collected from CALERIE participants. The goal was to explore gene expression changes brought about by caloric restriction over two years, compared to control groups.
To identify which human genes were impacted during calorie restriction, the scientists isolated messenger RNA (mRNA), a molecule that contains the code for proteins, from muscle samples. Isolating the protein sequence of each mRNA, they then used the information to identify which genes originated specific mRNAs.
Detailed analysis helped the researchers establish which genes during the calorie restriction process were ‘up-regulated’, meaning the cells made more mRNA, and which were ‘down-regulated’, meaning the cells produced less mRNA. The researchers were then able to confirm that calorie restriction affected the same gene pathways in humans, as in mice and non-human primates. A lower caloric intake upregulated genes which were responsible for energy generation and metabolism, and down-regulated inflammatory genes leading to lower inflammation.
Dr Ferrucci said, “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.”
