Emerging strategies, applications and challenges of targeting NAD+ in the clinic

Jianying Zhang; He-Ling Wang; Sofie Lautrup; Hilde Loge Nilsen; Jonas T. Treebak; Leiv Otto Watne; Geir Selbæk; Lindsay E. Wu; Torbjørn Omland; Eija Pirinen; Tin Cho Cheung; Jun Wang; Mathias Ziegler; Ole-Bjørn Tysnes; Rubén Zapata-Pérez; Santina Bruzzone; Carles Canto; Michela Deleidi; Georges E. Janssens; Riekelt H. Houtkooper; Morten Scheibye-Knudsen; Masaya Koshizaka; Koutaro Yokote; Eric Verdin; Vilhelm A. Bohr; Charalampos Tzoulis; David A. Sinclair; Evandro Fei Fang

doi:10.1038/s43587-025-00947-6

Emerging strategies, applications and challenges of targeting NAD+ in the clinic

Jianying Zhang
, He-Ling Wang
, Sofie Lautrup
, Hilde Loge Nilsen
, Jonas T. Treebak
, Leiv Otto Watne
, Geir Selbæk
, Lindsay E. Wu
, Torbjørn Omland
, Eija Pirinen
, Tin Cho Cheung
, Jun Wang
, Mathias Ziegler
, Ole-Bjørn Tysnes
, Rubén Zapata-Pérez
, Santina Bruzzone
, Carles Canto
, Michela Deleidi
, Georges E. Janssens
, Riekelt H. Houtkooper

Morten Scheibye-Knudsen, Masaya Koshizaka, Koutaro Yokote, Eric Verdin, Vilhelm A. Bohr, Charalampos Tzoulis, David A. Sinclair, Evandro Fei Fang^*

^*Corresponding author for this work

University of Oslo
Central South University
The Norwegian Centre on Healthy Ageing (NO-Age) and the Norwegian National Anti-Alzheimer's Disease (NO-AD) Networks
University of Copenhagen
Vestfold Hospital Trust
University of New South Wales
University of Oulu
University of Helsinki
Hong Kong Longevity Science Laboratory Limited
University of Bergen
Universidad Católica San Antonio de Murcia
University of Genoa
Swiss Federal Institute of Technology Lausanne
Université Sorbonne Paris Cité
University of Amsterdam
Chiba University
University of California at San Francisco
Buck Institute for Age Research
National Institutes of Health
Harvard University

Research output: Contribution to journal › Review article › Academic › peer-review

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Abstract

Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

Original language	English
Pages (from-to)	1704-1731
Number of pages	28
Journal	Nature Aging
Volume	5
Issue number	9
Early online date	2025
DOIs	https://doi.org/10.1038/s43587-025-00947-6
Publication status	Published - Sept 2025

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Zhang, J., Wang, H.-L., Lautrup, S., Nilsen, H. L., Treebak, J. T., Watne, L. O., Selbæk, G., Wu, L. E., Omland, T., Pirinen, E., Cheung, T. C., Wang, J., Ziegler, M., Tysnes, O.-B., Zapata-Pérez, R., Bruzzone, S., Canto, C., Deleidi, M., Janssens, G. E., ... Fang, E. F. (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging, 5(9), 1704-1731. https://doi.org/10.1038/s43587-025-00947-6

@article{246ef45bdd06462a9438dea581f4cc70,

title = "Emerging strategies, applications and challenges of targeting NAD+ in the clinic",

abstract = "Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.",

author = "Jianying Zhang and He-Ling Wang and Sofie Lautrup and Nilsen, \{Hilde Loge\} and Treebak, \{Jonas T.\} and Watne, \{Leiv Otto\} and Geir Selb{\ae}k and Wu, \{Lindsay E.\} and Torbj{\o}rn Omland and Eija Pirinen and Cheung, \{Tin Cho\} and Jun Wang and Mathias Ziegler and Ole-Bj{\o}rn Tysnes and Rub{\'e}n Zapata-P{\'e}rez and Santina Bruzzone and Carles Canto and Michela Deleidi and Janssens, \{Georges E.\} and Houtkooper, \{Riekelt H.\} and Morten Scheibye-Knudsen and Masaya Koshizaka and Koutaro Yokote and Eric Verdin and Bohr, \{Vilhelm A.\} and Charalampos Tzoulis and Sinclair, \{David A.\} and Fang, \{Evandro Fei\}",

note = "Publisher Copyright: {\textcopyright} Springer Nature America, Inc. 2025.",

year = "2025",

month = sep,

doi = "10.1038/s43587-025-00947-6",

language = "English",

volume = "5",

pages = "1704--1731",

journal = "Nature Aging",

issn = "2662-8465",

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Zhang, J, Wang, H-L, Lautrup, S, Nilsen, HL, Treebak, JT, Watne, LO, Selbæk, G, Wu, LE, Omland, T, Pirinen, E, Cheung, TC, Wang, J, Ziegler, M, Tysnes, O-B, Zapata-Pérez, R, Bruzzone, S, Canto, C, Deleidi, M, Janssens, GE , Houtkooper, RH, Scheibye-Knudsen, M, Koshizaka, M, Yokote, K, Verdin, E, Bohr, VA, Tzoulis, C, Sinclair, DA & Fang, EF 2025, 'Emerging strategies, applications and challenges of targeting NAD+ in the clinic', Nature Aging, vol. 5, no. 9, pp. 1704-1731. https://doi.org/10.1038/s43587-025-00947-6

TY - JOUR

T1 - Emerging strategies, applications and challenges of targeting NAD+ in the clinic

AU - Zhang, Jianying

AU - Wang, He-Ling

AU - Lautrup, Sofie

AU - Nilsen, Hilde Loge

AU - Treebak, Jonas T.

AU - Watne, Leiv Otto

AU - Selbæk, Geir

AU - Wu, Lindsay E.

AU - Omland, Torbjørn

AU - Pirinen, Eija

AU - Cheung, Tin Cho

AU - Wang, Jun

AU - Ziegler, Mathias

AU - Tysnes, Ole-Bjørn

AU - Zapata-Pérez, Rubén

AU - Bruzzone, Santina

AU - Canto, Carles

AU - Deleidi, Michela

AU - Janssens, Georges E.

AU - Houtkooper, Riekelt H.

AU - Scheibye-Knudsen, Morten

AU - Koshizaka, Masaya

AU - Yokote, Koutaro

AU - Verdin, Eric

AU - Bohr, Vilhelm A.

AU - Tzoulis, Charalampos

AU - Sinclair, David A.

AU - Fang, Evandro Fei

PY - 2025/9

Y1 - 2025/9

N2 - Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

AB - Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

UR - https://www.scopus.com/pages/publications/105015971091

U2 - 10.1038/s43587-025-00947-6

DO - 10.1038/s43587-025-00947-6

M3 - Review article

C2 - 40926126

SN - 2662-8465

VL - 5

SP - 1704

EP - 1731

JO - Nature Aging

JF - Nature Aging

IS - 9

ER -

Emerging strategies, applications and challenges of targeting NAD+ in the clinic

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