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

Research output: Contribution to journal › Letter › Research › peer-review

Standard

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. / Membrez, Mathieu; Migliavacca, Eugenia; Christen, Stefan; Yaku, Keisuke; Trieu, Jennifer; Lee, Alaina K.; Morandini, Francesco; Giner, Maria Pilar; Stiner, Jade; Makarov, Mikhail V.; Garratt, Emma S.; Vasiloglou, Maria F.; Chanvillard, Lucie; Dalbram, Emilie; Ehrlich, Amy M.; Sanchez-Garcia, José Luis; Canto, Carles; Karagounis, Leonidas G.; Treebak, Jonas T.; Migaud, Marie E.; Heshmat, Ramin; Razi, Farideh; Karnani, Neerja; Ostovar, Afshin; Farzadfar, Farshad; Tay, Stacey K.H.; Sanders, Matthew J.; Lillycrop, Karen A.; Godfrey, Keith M.; Nakagawa, Takashi; Moco, Sofia; Koopman, René; Lynch, Gordon S.; Sorrentino, Vincenzo; Feige, Jerome N.

In: Nature Metabolism, Vol. 6, No. 3, 2024, p. 433–447.

Research output: Contribution to journal › Letter › Research › peer-review

Harvard

Membrez, M, Migliavacca, E, Christen, S, Yaku, K, Trieu, J, Lee, AK, Morandini, F, Giner, MP, Stiner, J, Makarov, MV, Garratt, ES, Vasiloglou, MF, Chanvillard, L, Dalbram, E, Ehrlich, AM, Sanchez-Garcia, JL, Canto, C, Karagounis, LG, Treebak, JT, Migaud, ME, Heshmat, R, Razi, F, Karnani, N, Ostovar, A, Farzadfar, F, Tay, SKH, Sanders, MJ, Lillycrop, KA, Godfrey, KM, Nakagawa, T, Moco, S, Koopman, R, Lynch, GS, Sorrentino, V & Feige, JN 2024, 'Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia', Nature Metabolism, vol. 6, no. 3, pp. 433–447. https://doi.org/10.1038/s42255-024-00997-x

APA

Membrez, M., Migliavacca, E., Christen, S., Yaku, K., Trieu, J., Lee, A. K., Morandini, F., Giner, M. P., Stiner, J., Makarov, M. V., Garratt, E. S., Vasiloglou, M. F., Chanvillard, L., Dalbram, E., Ehrlich, A. M., Sanchez-Garcia, J. L., Canto, C., Karagounis, L. G., Treebak, J. T., ... Feige, J. N. (2024). Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. Nature Metabolism, 6(3), 433–447. https://doi.org/10.1038/s42255-024-00997-x

Vancouver

Membrez M, Migliavacca E, Christen S, Yaku K, Trieu J, Lee AK et al. Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. Nature Metabolism. 2024;6(3):433–447. https://doi.org/10.1038/s42255-024-00997-x

Author

Membrez, Mathieu ; Migliavacca, Eugenia ; Christen, Stefan ; Yaku, Keisuke ; Trieu, Jennifer ; Lee, Alaina K. ; Morandini, Francesco ; Giner, Maria Pilar ; Stiner, Jade ; Makarov, Mikhail V. ; Garratt, Emma S. ; Vasiloglou, Maria F. ; Chanvillard, Lucie ; Dalbram, Emilie ; Ehrlich, Amy M. ; Sanchez-Garcia, José Luis ; Canto, Carles ; Karagounis, Leonidas G. ; Treebak, Jonas T. ; Migaud, Marie E. ; Heshmat, Ramin ; Razi, Farideh ; Karnani, Neerja ; Ostovar, Afshin ; Farzadfar, Farshad ; Tay, Stacey K.H. ; Sanders, Matthew J. ; Lillycrop, Karen A. ; Godfrey, Keith M. ; Nakagawa, Takashi ; Moco, Sofia ; Koopman, René ; Lynch, Gordon S. ; Sorrentino, Vincenzo ; Feige, Jerome N. / Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. In: Nature Metabolism. 2024 ; Vol. 6, No. 3. pp. 433–447.

Bibtex

@article{910ae6b89e3e4bf4b4c55a5857c2142a,
title = "Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia",
abstract = "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.",
author = "Mathieu Membrez and Eugenia Migliavacca and Stefan Christen and Keisuke Yaku and Jennifer Trieu and Lee, {Alaina K.} and Francesco Morandini and Giner, {Maria Pilar} and Jade Stiner and Makarov, {Mikhail V.} and Garratt, {Emma S.} and Vasiloglou, {Maria F.} and Lucie Chanvillard and Emilie Dalbram and Ehrlich, {Amy M.} and Sanchez-Garcia, {Jos{\'e} Luis} and Carles Canto and Karagounis, {Leonidas G.} and Treebak, {Jonas T.} and Migaud, {Marie E.} and Ramin Heshmat and Farideh Razi and Neerja Karnani and Afshin Ostovar and Farshad Farzadfar and Tay, {Stacey K.H.} and Sanders, {Matthew J.} and Lillycrop, {Karen A.} and Godfrey, {Keith M.} and Takashi Nakagawa and Sofia Moco and Ren{\'e} Koopman and Lynch, {Gordon S.} and Vincenzo Sorrentino and Feige, {Jerome N.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s42255-024-00997-x",
language = "English",
volume = "6",
pages = "433–447",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

AU - Membrez, Mathieu

AU - Migliavacca, Eugenia

AU - Christen, Stefan

AU - Yaku, Keisuke

AU - Trieu, Jennifer

AU - Lee, Alaina K.

AU - Morandini, Francesco

AU - Giner, Maria Pilar

AU - Stiner, Jade

AU - Makarov, Mikhail V.

AU - Garratt, Emma S.

AU - Vasiloglou, Maria F.

AU - Chanvillard, Lucie

AU - Dalbram, Emilie

AU - Ehrlich, Amy M.

AU - Sanchez-Garcia, José Luis

AU - Canto, Carles

AU - Karagounis, Leonidas G.

AU - Treebak, Jonas T.

AU - Migaud, Marie E.

AU - Heshmat, Ramin

AU - Razi, Farideh

AU - Karnani, Neerja

AU - Ostovar, Afshin

AU - Farzadfar, Farshad

AU - Tay, Stacey K.H.

AU - Sanders, Matthew J.

AU - Lillycrop, Karen A.

AU - Godfrey, Keith M.

AU - Nakagawa, Takashi

AU - Moco, Sofia

AU - Koopman, René

AU - Lynch, Gordon S.

AU - Sorrentino, Vincenzo

AU - Feige, Jerome N.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s42255-024-00997-x

DO - 10.1038/s42255-024-00997-x

M3 - Letter

C2 - 38504132

AN - SCOPUS:85188126464

VL - 6

SP - 433

EP - 447

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 3

ER -

ID: 386304954