Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

Mathieu Membrez, Eugenia Migliavacca, Stefan Christen, Keisuke Yaku, Jennifer Trieu, Alaina K. Lee, Francesco Morandini, Maria Pilar Giner, Jade Stiner, Mikhail V. Makarov, Emma S. Garratt, Maria F. Vasiloglou, Lucie Chanvillard, Emilie Dalbram, Amy M. Ehrlich, José Luis Sanchez-Garcia, Carles Canto, Leonidas G. Karagounis, Jonas T. Treebak, Marie E. MigaudRamin Heshmat, Farideh Razi, Neerja Karnani, Afshin Ostovar, Farshad Farzadfar, Stacey K.H. Tay, Matthew J. Sanders, Karen A. Lillycrop, Keith M. Godfrey, Takashi Nakagawa, Sofia Moco, René Koopman, Gordon S. Lynch, Vincenzo Sorrentino*, Jerome N. Feige*

*この論文の責任著者

研究成果: ジャーナルへの寄稿Letter査読

16 被引用数 (Scopus)

抄録

Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1–3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.

本文言語英語
ページ(範囲)433-447
ページ数15
ジャーナルNature Metabolism
6
3
DOI
出版ステータス出版済み - 2024/03

ASJC Scopus 主題領域

  • 内科学
  • 内分泌学、糖尿病および代謝内科学
  • 生理学(医学)
  • 細胞生物学

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