Coffee molecule may improve aging muscles

By Staff 9 Min Read

  • Sarcopenia, which is the progressive loss of muscle mass and strength, affects many adults when they get older.
  • The loss of muscle mass can contribute to mobility problems, frailty, and subsequent reduction in independence for many older people.
  • Researchers, including from Nestle Research, found that a compound found in coffee and fenugreek, but also made in the microbiome in the gut, improves energy metabolism in muscle fibers in humans, mice, and worms.

Sarcopenia describes the loss of skeletal muscle that occurs naturally as we age.

Approximately 10%-16% of people over the age of 65 are thought to be affected worldwide, and prevalence is higher in people with other conditions, for example, cancer and diabetes.

It is a natural part of aging, and the average adult loses about 250g of muscle each year between the ages of 30 and 60, and this accelerates after the age of 70.

This can lead to mobility problems, falls and frailty that often leads to a loss of independence in older people. As such, it represents a significant disease burden in an aging population.

A recent study looking at worms, male mice and tissue samples taken from male participants affected by sarcopenia, investigated the molecular mechanisms underpinning this condition.

They found that a compound found in coffee and fenugreek, but also made in the microbiome in the gut, can improve muscle function in aging humans, mice, and worms.

The results were published in a letter to Nature Metabolism.

Dr. Kubanych Takyrbashev the Health and Wellness Advisor at NAO, who has previously worked as a doctor specializing in critical care of older adults, who was not involved in the study, explained to Medical News Today how sarcopenia affects aging humans:

“One of the most concerning implications of sarcopenia is the increased risk of falls and fractures. Declining muscle mass and strength contribute to decreased mobility and agility, making individuals more susceptible to accidents. Additionally, sarcopenia often leads to functional decline and disability, impairing activities of daily living and diminishing independence. Many individuals with sarcopenia require assistance for routine tasks, which can significantly impact their quality of life.”

Past research has indicated that people who engage in physical exercise are less likely to develop sarcopenia. Poor nutrition including not eating enough protein is also associated with sarcopenia. However, there are few interventions other than these that can be recommended for people affected.

The condition also tends to affect men more than women, and this is thought to be due to loss of testosterone as they age.

“Although sarcopenia can affect both men and women, my observations suggest that men might experience a higher prevalence of sarcopenia due to factors such as hormonal changes and decreased physical activity. Sarcopenia usually becomes problematic after the age of 50, but early signs of muscle weakness can be detectable before age 50, highlighting the importance of preventive measures. Advancing age is a primary risk factor for sarcopenia,” Dr. Takyrbashev said.

In this study, an international team of researchers looked specifically at the role of oxidized nicotinamide adenine dinucleotide (NAD+) levels, on sarcopenia.

NAD+ is a coenzyme involved in metabolism in all cells in eukaryotic organisms. It is involved in redox reactions in the Krebs cycle and glycolysis, for example. It is present in the mitochondria where it plays an important role in energy homeostasis.

Previous research by these scientists had shown that low levels of it, along with lower mitochondrial energy production, were associated with greater skeletal muscle aging and sarcopenia.

Many members of the team are based at food-manufacturer Nestle-owned Nestle Research in Lausanne, Switzerland.

The researchers analyzed serum levels of 20 male Chinese individuals ages 65-79 with sarcopenia and age-matched healthy controls and found patients with sarcopenia had lower circulating concentrations of trigonelline, a chemical found in plants and animals.

Upon further analysis, the researchers found that trigonelline levels were positively associated with muscle mass, grip strength, and gait speed, and higher levels of NAD+ in skeletal muscle. They saw similar results in another cohort.

Tissue samples were exposed to trigonelline in vitro, and researchers found myotubes, a type of tissue found in the muscles, had raised NAD+ levels when treated with trigonelline, but other muscle cells, liver cells, and kidney cells did not. Treating muscle tissue samples from participants and aged-matched healthy controls with trigonelline raised NAD+ levels in both.

Worms were then treated with trigonelline on day one of adulthood and experienced an extended lifespan compared to controls. They also showed increased mitochondrial respiration.

The researchers gave male older (20 months old) mice a dietary supplement of trigonelline, and a 5-day course improved mitochondrial activity in the mice. A 12-week course of supplementation increased plasma, liver and muscle levels of trigonelline, compared to controls. Further experiments showed that grip strength increased in mice given trigonelline supplementation, compared to controls.

The authors suggest that the findings show that rather than changing the structure of muscle fibers, trigonelline improves mitochondrial activity in these cells.

The authors make the point that trigonelline is present in coffee and fenugreek. They cited research that shows that higher levels of caffeine are associated with lower levels of sarcopenia in Korea but said their own analysis showed this association is not found in the Middle East. They suggest this could be due to low coffee consumption there.

Nestle owns the Nescafe coffee brand.

A spokesperson from Nestle Research, Katharina Fischer, R&D Scientific Communications Manager told Medical News Today:

“Trigonelline is an endogenous metabolite both in women and men and NAD and mitochondrial metabolism are conserved between sexes. In this study, our work has mainly focused on male subjects for technical and clinical feasibility reasons, although some female subjects were also included in a small subset of the experiments. The conclusions of the study are therefore most likely applicable to both men and women.”

The researchers also found that dietary fiber and folate were associated with higher trigonelline levels in the body, and explained that the compound could also be made in the gut due to the actions of the microbiome.

“As reported in the paper, our clinical dietary modeling analysis identified links between dietary fiber and folate intake and trigonelline levels in the human body. While these signals open new opportunities to modulate endogenous trigonelline production, we focused the work on providing trigonelline orally given its high abundance in certain foods like fenugreek or coffee,” Fischer explained.

“The work opens new translational opportunities to test the clinical efficacy of increasing trigonelline consumption and to develop food products enriched in trigonelline for muscle health. The importance of maintaining NAD levels in other organs during aging also opens applications to other health benefits for healthy longevity,” she added.

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