Natural molecule boosts NAD+ levels, improving muscle function during aging

Trigonelline, which can be found in coffee, declines during sarcopenia – but increasing its levels can improve physical performance.

Sarcopenia, a condition characterized by the progressive loss of skeletal muscle mass and function, poses a substantial global health challenge, particularly among the growing elderly population.

Now recent research from Nestlé Research in Switzerland and the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), in collaboration with other academic institutions, sheds light on a potential therapeutic avenue involving the natural molecule trigonelline [1]. Trigonelle, which is found in the body, is also readily available from dietary sources such as coffee and fenugreek seeds.

Longevity.Technology: Central to the pathophysiology of sarcopenia are cellular alterations associated with aging, including diminished mitochondrial function and a decline in nicotinamide adenine dinucleotide (NAD+) levels. These changes contribute to the deterioration of muscle tissue and functional decline, and, notably, the research consortium identified a correlation between reduced trigonelline levels and sarcopenia in aging individuals.

In preclinical models, the administration of trigonelline demonstrated efficacy in mitigating aspects of sarcopenia. Specifically, trigonelline supplementation resulted in elevated NAD+ levels, enhanced mitochondrial activity, and preservation of muscle function. These findings, say the authors, suggest that nutritional supplementation of trigonelline could serve as a NAD+ boosting strategy that works to attenuate age-related muscle decline [1].

Natural molecule boosts NAD+ levels, improving muscle function during aging
Trigonelline (top bubble) has been found to decline during sarcopenia. It can improve physical performance during aging by enhancing NAD+ levels (middle bubble) and mitochondrial activity (lowest bubble).

The research also showed that trigonelline supplementation in C elegans was associated with improved mitochondrial respiration and biogenesis, reduced muscle wasting and increased lifespan and mobility in animal models, mediated through an NAD+-dependent mechanism involving sirtuin pathways. Supplementing the diets of male mice with trigonelline enhanced their muscle strength and prevented fatigue during aging. [1].

The research findings underscore the therapeutic potential of trigonelline supplementation in addressing sarcopenia. While popping to Starbucks won’t help in the short term, trigonelline offers a promising avenue for intervention against age-associated muscle decline. Moreover, the identification of trigonelline as a modulator of NAD+ levels highlights its importance in cellular metabolism and aging processes.

Assistant Professor Vincenzo Sorrentino from the Healthy Longevity Translational Research Programme at NUS Medicine and corresponding author on the paper said: “Our findings expand the current understanding of NAD+ metabolism with the discovery of trigonelline as a novel NAD+ precursor and increase the potential of establishing interventions with NAD+-producing vitamins for both healthy longevity and age-associated diseases applications [2].”

Nutrition and physical activity are important lifestyle recommendations to maintain healthy muscles during aging. “We were excited to discover through collaborative research that a natural molecule from food cross-talks with cellular hallmarks of ageing. The benefits of trigonelline on cellular metabolism and muscle health during ageing opens promising translational applications,” said Jerome Feige, Head of the Physical Health department at Nestlé Research [2].

Sarcopenia represents a significant global health burden, with profound implications for both individual well-being and healthcare systems worldwide. The discovery of trigonelline’s role in modulating cellular pathways associated with sarcopenia opens the door on a potential means of intervention, and further research that elucidates the precise mechanisms of trigonelline action and its clinical utility is warranted. Coffee-flavored fenugreek seeds, anyone?

Image courtesy of Yong Loo Lin School of Medicine, NUS

[1] https://www.nature.com/articles/s42255-024-00997-x
[2] https://medicine.nus.edu.sg/news/natural-molecule-found-in-coffee-and-human-body-increases-nad-levels-improves-muscle-function-during-ageing/