Calorie restriction stimulates muscle health & healthy aging genes

A new study has investigated the biological mechanisms brought about by calorie restriction and found that a moderate reduction in calorie intake can improve muscle health and activate biological pathways important for good health.

Decreasing caloric intake without depriving the body of essential nutrients – known as calorie restriction – has been shown in animal models to positively affect skeletal muscle and delay the progression of age-related diseases. However, little information has been gathered on the long-term health effects of calorie restriction on humans.

Researchers from the US National Institutes of Health (NIH) analyzed the biological mechanisms underpinning calorie restriction to see whether they led to the same positive health effects in humans as those seen in animals.

Analyzing data 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 the participants were able to achieve was a reduction of 12%. Nonetheless, this moderate reduction was enough to activate most biological pathways associated with healthy aging.

“A 12% reduction in calorie intake is very modest,” said Luigi Ferrucci, corresponding author of the study. “This kind of small reduction in calorie intake is doable and may make a big difference in your health.”

The researchers performed comprehensive RNA 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 controls.

Ninety participants consented to a thigh muscle biopsy, taken pre-study and at one- and two-year follow-ups over the study period. The researchers isolated messenger RNA (mRNA) from the samples and determined the protein sequence of each mRNA. They used this information to identify which genes originated specific mRNAs and determined the genes that were upregulated and those that were downregulated in calorie-restricted participants.

The researchers confirmed that calorie restriction affected the same gene pathways in humans as it did in mice and non-human primates. They identified that gene expression was significantly changed in calorie-restricted participants compared to controls, including genes related to protein regulation, circadian rhythm regulation, DNA repair, programmed cell death (apoptosis), and inflammation.

There were changes in biological pathways involved in muscle repair and skeletal muscle formation (myogenesis), leading to an increase in skeletal muscle quality and the mechanisms of aging. Some upregulated genes included those responsible for energy generation and metabolism, while downregulated inflammatory genes reduced inflammation.

The researchers say their findings highlight the mechanisms by which calorie restriction provides health benefits, especially in older people.

“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,” Ferrucci said.

The study was published in the journal Aging Cell.

Source: National Institutes of Health

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