Small restrictions, big benefits: Calorie restriction supports healthy aging and muscle health, experts reveal

18 Oct 2023 --- Researchers at the US National Institutes of Health suggest that reducing overall calorie intake may benefit muscle health. Over the course of two years, participants who restricted their calories by 12% without depriving the body of essential vitamins and minerals activated most biological pathways essential to healthy aging. 

Although the researchers found that sustained calorie restriction did induce minor leg lean mass losses, they revealed that muscle strength remained unchanged. Additionally, it improved skeletal muscle quality and impacted gene expression and splicing profiles of biological pathways affected by reducing calorie intake. 

“A 12% reduction in calorie intake is very modest,” says Dr. Luigi Ferrucci, co-author of the study and scientific director at the National Institute on Aging. “This small reduction in calorie intake is doable and may make a big difference in your health.”

For example, lower caloric intake upregulated genes responsible for energy generation and metabolism while decreasing inflammation. 

“Since inflammation and aging are strongly coupled, calorie restriction represents a powerful approach to preventing the pro-inflammatory state developed by many older people,” explains Ferrucci.

CALERIE project 
In animal studies, calorie restriction has been known to delay the progression of age-related diseases. The new research, published in Aging Cell, suggests the same applies to humans. 

The study analyzed data from 90 participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), a two-phase trial to test the effects of caloric restriction in humans. 

By restricting their calories by 12%, study participants activated biological pathways essential to healthy aging.In CALERIE’s first phase, researchers assessed the feasibility and safety of a more extended study. Its second phase consisted of a two-year controlled trial in young and middle-aged, non-obese, healthy men and women. One group reduced calorie intake, while the control group was not restricted in its diet. 

Although CALERIE aimed to reduce daily caloric intake by 25%, the highest group reached a sustained reduction of 12% during two years, resulting in a 10% sustained weight loss. 

Genetic pathways 
According to the research team, calorie restriction affected the same gene pathways in humans as in mice and non-human primates, as determined in earlier research. 

Through a linear effect model, the research team identified protein-coding genes and splicing variants whose expression was significantly changed in the group restricting calories compared to the control group. 

The researchers used thigh muscle biopsies collected from CALERIE participants when individuals joined the study and at one-year and two-year follow-ups. They isolated messenger RNA (mRNA) — a molecule that contains the code for proteins — from the collected muscle samples. By identifying the protein sequence of these molecules, they determined which genes originated from specific mRNA. 

Genes that were significantly changed in the calorie restriction group included those related to proteostasis — regulating protein within the cell to maintain health — circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing or splicing, Forkhead box O3 metabolism (associated with human longevity), apoptosis or cell death and inflammation. 

Healthy aging developments 
The healthy aging market experiences strong growth. Data from Innova Market Insights indicate that functional foods and beverages with “aging well” claims grew by 14% annually globally from 2018 to 2022. 

At the same time, the UN has declared the decade from 2021 to 2030 “The Decade of Healthy Aging.” Industry experts note that the demand for healthy aging products stems from an increasingly aging population and a wish to stay healthy and independent as long as possible.

Companies are also recognizing the opportunities of AI in anti-aging and gene treatment, as well as the potential of DNA methylation tests to determine someone’s biological age. 

Meanwhile, there is a growing body of research on the impact of lifestyle and diet interventions on healthy aging. For example, an eight-week program successfully reduced women’s biological age by an average of 4.6 years through diet, sleep, exercise, relaxation guidance, supplements, nutritional coaching and consuming epi nutrients. 

By Jolanda van Hal