The Power of Caloric Intake: Enhancing Muscle Health and Longevity
Caloric restriction (CR) is a dietary approach where calorie intake is reduced without malnutrition. In rodents, a 40% reduction in calorie intake has been shown to extend lifespan, delay disease onset, and improve the body's ability to handle stress. The CALERIE study delved into the effects of a 12% CR over two years in healthy humans. The results? Minor muscle mass loss without any decline in muscle strength. But how does this work? Deep dives into the muscle tissues of participants revealed changes in the expression of genes linked to various processes like DNA repair, mitochondrial creation, and inflammation. These changes hint at the preservation of muscle quality and suggest that even moderate CR can have profound benefits on muscle health and overall longevity in humans.
Article Information
Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study
Published on Aging Cell. Jayanta Kumar Das et al.
Abstract
The lifespan extension induced by 40% caloric restriction (CR) in rodents is accompanied by postponement of disease, preservation of function, and increased stress resistance. Whether CR elicits the same physiological and molecular responses in humans remains mostly unexplored. In the CALERIE study, 12% CR for 2 years in healthy humans induced minor losses of muscle mass (leg lean mass) without changes of muscle strength, but mechanisms for muscle quality preservation remained unclear. We performed high-depth RNA-Seq (387-618 million paired reads) on human vastus lateralis muscle biopsies collected from the CALERIE participants at baseline, 12- and 24-month follow-up from the 90 CALERIE participants randomized to CR and "ad libitum" control. Using linear mixed effect model, we identified protein-coding genes and splicing variants whose expression was significantly changed in the CR group compared to controls, including genes related to proteostasis, circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing/splicing, FOXO3 metabolism, apoptosis, and inflammation. Changes in some of these biological pathways mediated part of the positive effect of CR on muscle quality. Differentially expressed splicing variants were associated with change in pathways shown to be affected by CR in model organisms. Two years of sustained CR in humans positively affected skeletal muscle quality, and impacted gene expression and splicing profiles of biological pathways affected by CR in model organisms, suggesting that attainable levels of CR in a lifestyle intervention can benefit muscle health in humans.
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