Researchers at the National Institutes of Health have published a study in the journal " Aging Cell" entitled " Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study".
The study shows that a 12% reduction in daily caloric intake is sufficient to activate most of the biological pathways that are critical for healthy aging, which can build muscle and slow aging.
In addition, the biological pathways that calorie restriction exerts in humans are consistent with those previously found in animal models.
In this study, researchers analyzed data from the Comprehensive Assessment of the Long-Term Effects of Reducing Energy Intake (CALERIE) randomized controlled trial, a National Institutes of Health-funded clinical trial that was the first randomized controlled study of caloric restriction in healthy humans.
To elucidate the mechanisms by which CR improves muscle health, researchers analyzed 90 participants in CALERIE 2, including 31 men and 59 women, randomly divided into 2 groups: a caloric restriction group (CR, 57 people), and an ad libitum eating group (AL, 33 people). Skeletal muscles of the participants were collected and comprehensive RNA sequencing analyses were performed to analyze gene expression changes that occurred over 12 and 24 months in both groups.
Overall, participants in both groups were healthy at enrollment, with a mean age of 38 years in the CR group and 40 years in the AL group, and muscle biopsies were performed at 12 and 24 months, with an average 12% reduction in daily caloric intake in the CR group over the 2-year study period.
Participants in the CR group lost a significant amount of weight, an average of 9 kg, at the 12th month examination, but did not lose any further weight over the following 12 months, whereas participants in the AL group maintained a stable weight.
Interestingly, although participants in the CR group lost muscle mass, they did not lose muscle strength, and there was no significant difference in absolute muscle strength in the CR group compared with the AL group. This suggests that caloric restriction increased the amount of force produced per unit of muscle mass.
Muscle strength differences
Further, the researchers biopsied 162 muscle samples from 90 participants and isolated 60,605 messenger RNAs (mRNAs) from the samples and analyzed the differential changes in gene expression between the CR and AL groups.
It was found that caloric restriction up-regulated the expression of 171 genes and down-regulated the expression of 28 genes that have been shown to be affected by CR in animal models and are considered to be markers of aging, compared to AL.
Specifically, genes related to complexes that protect telomeres, autophagy, integrated stress response, DNA damage repair, muscle growth and repair were upregulated, and inflammation-related genes were downregulated.
Downregulation of inflammation-related genes
Finally, gene set enrichment analysis revealed that calorie restriction exerts a biological pathway in humans that is consistent with what has been previously found in animal models, supporting the concept that calorie restriction enhances anti-aging mechanisms.
The researchers say that this study demonstrates, for the first time, that calorie restriction in humans exerts a molecular pathway consistent with animal models to maintain skeletal muscle health and down-regulate inflammatory genes, and that since inflammation and aging are closely linked, restricting calorie intake is an effective way of preventing the pro-inflammatory state that occurs in many older adults.
In summary, the results suggest that caloric restriction strengthens muscle and activates biological pathways critical to health, contributing to a long and healthy life.
