Calorie restriction has long been recognized as a practice that can improve overall health. Recent research has delved into the effects of calorie restriction on muscle quality in humans, drawing from the CALERIE study conducted several years ago. This study revealed that even modest calorie restriction yielded significant improvements in markers of muscle quality, paralleling previous findings from animal studies.
The focus of the CALERIE study was to determine whether the physiological and molecular responses observed in rodents subjected to caloric restriction would also be observed in humans. While the study involved a relatively mild 12% calorie restriction over a period of two years, it did result in minor losses of muscle mass without affecting muscle strength. However, the mechanisms underlying the preservation of muscle quality remained unclear.
To shed light on this matter, researchers performed high-depth RNA-Seq analysis on muscle biopsies taken from participants in the CALERIE study. These biopsies were collected at baseline, as well as at the 12- and 24-month follow-ups. The analysis involved comparing the gene expression and splicing profiles of the calorie-restricted group to those of the control group who ate an unrestricted diet (“ad libitum”).
Through this analysis, the researchers identified significant changes in the expression of protein-coding genes and splicing variants in the calorie-restricted group compared to the control group. These changes encompassed a wide range of biological pathways, including proteostasis (protein homeostasis), circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing and splicing, FOXO3 metabolism, apoptosis, and inflammation.
Interestingly, alterations in some of these biological pathways were found to mediate the positive effect of calorie restriction on muscle quality. Moreover, the differentially expressed splicing variants were associated with changes in pathways previously shown to be affected by calorie restriction in model organisms.
Taken together, the findings indicate that two years of sustained calorie restriction can have a beneficial impact on skeletal muscle quality in humans. Furthermore, the gene expression and splicing profiles observed in this study align with those affected by calorie restriction in animal models. This suggests that implementing attainable levels of calorie restriction through lifestyle interventions can indeed promote muscle health in humans.
This study adds to the growing body of evidence supporting the benefits of calorie restriction for human health. By demonstrating its positive effects on muscle quality, it highlights a potential avenue for improving overall physical well-being. Although further research is needed to fully understand the underlying mechanisms, these findings pave the way for future interventions aimed at enhancing muscle health through targeted dietary modifications.
