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Study finds natural molecule in coffee and human body increases NAD+ levels, improves muscle function during aging

Natural molecule found in coffee and human body increases NAD+ levels, improves muscle function during aging
Serum trigonelline is reduced in human sarcopenia and is associated with mitochondrial and NAD+ metabolism in skeletal muscle. a, Serum levels of trigonelline in healthy controls (n = 20) and individuals with sarcopenia (n = 20) from the MEMOSA SSS (unpaired, two-tailed Student’s t-test). b, Association of serum trigonelline levels with ALMI, grip strength and gait speed; the Pearson correlation coefficient and its P value were calculated on n = 40 serum samples from the SSS. c, SSS muscle RNA-seq association with serum trigonelline levels. Gene set enrichment ordered according to the significance of enrichment with only the top ten gene sets being reported. A false discovery rate (FDR) < 1020 was trimmed at FDR = 1020 (n = 39 muscle samples). d, Enrichment plot for the hallmark oxidative phosphorylation gene set from c. e,f, Relative NAD+ levels in HSMMs after treatment with increasing concentrations of trigonelline, in the absence (e) or presence (f) of FK866 (one-way analysis of variance (ANOVA), mean ± s.e.m, n = 6 biological replicates per group). g, Relative NAD+ levels in human primary myotubes from healthy controls and patients with sarcopenia from the Hertfordshire Sarcopenia Study Extension (HSSe) cohort treated ex vivo with or without trigonelline (unpaired, two-tailed Student’s t-test, mean ± s.e.m, n = 3 biological replicates per group). h, Relative NAD+ levels in primary myotubes from aged mice (22 months) treated ex vivo with trigonelline (unpaired, two-tailed Student’s t-test, mean ± s.e.m, n = 8 and n = 9 biological replicates per group). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Credit: Nature Metabolism (2024). DOI: 10.1038/s42255-024-00997-x

A research consortium led by Nestlé Research in Switzerland and the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) made a recent discovery that the natural molecule trigonelline present in coffee, fenugreek, and also in the human body, can help to improve muscle health and function.

In an among the University of Southampton, University of Melbourne, University of Tehran, University of South Alabama, University of Toyama, and University of Copenhagen, the work builds on a previous collaborative study that described novel mechanisms of human sarcopenia.

Sarcopenia is a condition where cellular changes that happen during aging gradually weaken the muscles in the body and lead to accelerated loss of muscle mass and strength and reduced physical independence.

One important problem during sarcopenia is that the cellular cofactor NAD+ declines during aging, while mitochondria, the energy powerhouses in our cells, produce less energy. The study team discovered that levels of trigonelline were lower in older people with sarcopenia.

Providing this molecule in pre-clinical models resulted in increased levels of NAD+, increased mitochondrial activity, and contributed to the maintenance of muscle function during aging.

NAD+ levels can be enhanced with different dietary precursors like the essential amino acid L-tryptophan (L-Trp), and vitamin B3 forms such as nicotinic acid (NA), nicotinamide (NAM), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).

Assistant Professor Vincenzo Sorrentino from the Healthy Longevity Translational Research Program at NUS Medicine added, "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."

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

The study is published in the journal Nature Metabolism.

More information: Mathieu Membrez et al, Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia, Nature Metabolism (2024). DOI: 10.1038/s42255-024-00997-x

Citation: Study finds natural molecule in coffee and human body increases NAD+ levels, improves muscle function during aging (2024, March 21) retrieved 22 July 2024 from
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