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Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle
Open accessAbstract
NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function.
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“Reduced NAD+ levels in skeletal muscle of aged or Nampt deficient mice alter mitochondrial bioenergetics and impair muscle mass, strength and endurance49,50,52,53”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [52]
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1 retracted
Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats
Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019194 · Cited by 594
RetractedCantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210
Cárdenas, C., Miller, R. A., Smith, I., Bui, T., Molgó, J., Müller, M., Vais, H., Cheung, K.-H., Yang, J., Parker, I., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.007 · Cited by 1,026
Geriatric muscle stem cells switch reversible quiescence into senescence
Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A. L., et al. (2014) · Nature · doi:10.1038/nature13013 · Cited by 1,010
Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion
Ha, H. C., & Snyder, S. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13978 · Cited by 913
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Zhang, L., Yan, Y. R., Li, S. Q., Lin, Y. N., Wang, Y., Wang, Y. Q., Li, N., Lu, F., Sun, X. W., Zhang, L. Y., et al. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13693 · Cited by 3
Zhou, C., & Ying, W. (2021) · PeerJ · doi:10.7717/peerj.11401 · Cited by 2
“deficiency also appears to play an important role in the aging process (Frederick et al., 2016; Mills et al., 2016; Son et al., 2016), which has been the biological basis for the wide applications of NAD and NAD precursors for delaying aging.”
BackgroundMolecular physiological studies on health effects of dietary nicotinamide riboside, a vitamin B3
Shi, W. (2019) · doi:10.18174/471911 · Cited by 2
NAD+ flux is maintained in aged micePreprint
McReynolds, M. R., Chellappa, K., Chiles, E. N., Jankowski, C. S. R., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Chu, Q., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-86538/v1 · Cited by 2
Self-citationBlomquist, S. A., Kelly, G., Adães, S., D’Adamo, C. R., Ardagh, A., Ramer, S., & Scuba, W. (2025) · medRxiv · doi:10.1101/2025.05.14.25327611 · Cited by 2
Palikhe, S., & Nakagawa, T. (2022) · Springer eBooks · doi:10.1007/978-981-16-7977-3_8 · Cited by 1
Nicotinamide Adenine Dinucleotide and Aging
Jiang, Z., Luo, L., Qin, Y., Huang, Y., & Yan, S. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_28 · Cited by 1
Piceatannol Enhances Intracellular Energy Metabolism via SIRT1 in C2C12 Cells
Tsuda, H., Uchida, T., Okuno, S., Ulla, A., Kawakami, S., Mori, S., Maruki‐Uchida, H., & Nikawa, T. (2025) · Advances in Biological Chemistry · doi:10.4236/abc.2025.153005 · Cited by 1
Muscle needs NAD, but how much?
Frederick, D. W., McGaunn, J. P., & Baur, J. A. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.06.001 · Cited by 1
Self-citationLi, L., Wang, R., Zhu, J., Cao, F., Min, J., Ouyang, D., & Lin, L. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.109296 · Cited by 1
Karim, M., Yaku, K., Kim, J., Okekawa, A., Wada, T., Uchida, H., MIZUTANI, A., Nguyen, T. C. T., Kawaguchi, Y., Nakagawa, Y., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116912 · Cited by 1
Swain, A., Soni, N. D., Gaspar, R. B., Davis, J. G., Liu, F., Juul, H. M., Nanga, R. P. R., Baur, J. A., & Reddy, R. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-01958-0 · Cited by 1
“The dosage was selected based on prior studies showing physiologically meaningful effects of NR supplementation in mice and is consistent with the dosage used in AD mouse models [24, 25].”
Self-citationLiu, A., Zhu, X., Sun, W.-D., Bi, S.-Z., Zhang, C., & Li, J. N. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112688 · Cited by 1
NAMPT beyond NAD+ biosynthesis: roles in tumor microenvironment remodeling and cancer progression
Sun, W.-D., Bi, S.-Z., Zhu, X., Lai, S.-Y., Zhang, C., Liu, A., & Li, J.-H. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118344 · Cited by 2
Finger, F., Frost, M., Watanabe, S., Ma, T., Kang, T., Biswas, D., Perez, R. Z., Anton, V., Dollet, L., Markussen, L. K., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01227-7 · Cited by 2
Self-citationLundt, S., & Ding, S. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290893 · Cited by 1
“Skeletal muscles are atrophied, are significantly weaker, and seem to be degenerating (Frederick et al., 2016).”
Potential significance of NAD+ biology translational research in super-aged Japan
山口慎太郎, 裕, 伊., & 純, 吉. (2020) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.57.213 · Cited by 1
烟酰胺腺嘌呤二核苷酸（NAD+）合成代谢及其调控机体衰老研究进展
Li, Y., Tian, X., Luo, J., Bao, T., & Wu, X. (2024) · Scientia Sinica Vitae · doi:10.1360/ssv-2024-0004
Chen, Y., Liu, Z., Chen, L., Yang, D., Xiao, M., Li, Z., & Xie, Z. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5569 · Cited by 1
“Reduced NAD + levels in aged skeletal muscle alter mitochondrial bioen‑ ergetics and have a negative effect on muscle mass, strength and endurance (33,34), indicating that low NAD + contributes to impaired mitochondrial activity and promotes progression of muscle atrophy.”
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Meiliana, A., Dewi, N. M., & Wijaya, A. (2021) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v13i4.1655
“Supplementing with the NAD+ precursor nicotinamide riboside can also help to reverse increasing muscle dysfunction.(94) Finally, it has recently been discovered that exercise protects against age-related secondary damage by preventing mitochondrial respiration decreases.”
BackgroundConnell, N. J. (2021) · Research Publications (Maastricht University) · doi:10.26481/dis.20210122nc · Cited by 1
Intravenous Uptake of NMN is Safely Metabolize and Increases NAD+ Levels in Healthy SubjectsPreprint
Kimura, S., Ichikawa, M., Sugawara, S., Katagiri, T., Hirasawa, Y., Ishikawa, T., Matsunaga, W., & Gotoh, A. (2022) · Research Square · doi:10.21203/rs.3.rs-1298321/v1 · Cited by 1
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Kyriazis, G. A., Serrano, J., Boyd, J., Mason, C., Smith, K., Károlyi, K., Kondo, S., Brown, I., Maurya, S. K., Meshram, N. N., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2475555/v1 · Cited by 1
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Irazoki, A., Frank, E., Pham, T. C. P., Braun, J. L., Ehrlich, A. M., Haid, M., Riols, F., Hansen, C. H. F., Jørgensen, A.-S. R., Andersen, N. R., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.29.596034 · Cited by 1
“Absolute force measurements were normalized to muscle cross sectional area to find the specific force (muscle mass divided by the product of the muscle density coefficient (1.06 g/cm 3 ), optimal muscle length, and the muscle-specific fiber length coefficient (0.71 for soleus 33 ).”
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Lima, V. M. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2017.tde-07032017-100454
Vitamin B3 salvage and NAD\(^+\) metabolism in skeletal muscle
Fletcher, R. S. (2017) · University of Birmingham Institutional Research Archive (University of Birmingham)
Doig, C. L., Zielinska, A. E., Fletcher, R. S., Oakey, L. A., Elhassan, Y., Garten, A., Cartwright, D., Heising, S., Alsheri, A., Watson, D. G., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/567297
The Effects of Exercise on LINE-1 Regulation
Romero, M. A. (2019)
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Passarge, M., & Schütz, B. (2021) · Journal für Gynäkologische Endokrinologie/Schweiz · doi:10.1007/s41975-021-00184-1
Fu, Z., Li, L., Xia, Y., Yao, B., Liu, Y., & Ding, H. (2022) · Research Square · doi:10.21203/rs.3.rs-1925619/v1
Metabolic precursors of nicotinamide adenine dinucleotide and the potential for their clinical use
Sutsko, I. P., Shlyahtun, A. H., & Semenenya, I. N. (2022) · Medical academic journal · doi:10.17816/maj89964
Metabolites and metabolomics in COVID-19
Gowda, D., Kellarai, A., Hegde, P. S., Agni, M. B., Lundstrom, K. H., & Barh, D. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91794-0.00026-3
Stan, T. L., Vijver, D. V. D., Verhaart, I. E. C., & Aartsma-Rus, A. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.02.526793
“However, as stated before, we have used a concentration recommended and previously used by others [49, 51, 62] and increasing the NR dose is not an option due to tolerability issues.”
InfluentialBai, X., & Wang, P. (2021) · Research Square · doi:10.21203/rs.3.rs-961019/v1
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Lundt, S. (2023) · MOspace Institutional Repository (University of Missouri) · doi:10.32469/10355/96990
Chinen, N., Otsu, W., Kuse, Y., Nakamura, S., Hara, H., & Shimazawa, M. (2024) · BPB Reports · doi:10.1248/bpbreports.7.6_211
Chen, Y., Liu, Z., Chen, L., Yang, D., & Xie, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-5416107/v1
Strategies to Overcome Metabolic Syndrome and Related Diseases
(2025) · Frontiers research topics · doi:10.3389/978-2-8325-5556-9
Coenzyme I and Skeletal Muscle Disorders
Jiang, Z., Luo, L., Qin, Y., Zhou, Y., & Zhao, F. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_30
Nicotinamide Adenine Dinucleotide and Signaling Transduction
Xu, H., Zhang, D., Sun, M., & Qin, Z.-H. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_17
Kong, B. S., L’Yi, S., Ramirez-Hernandez, E. G., Hong, S., Weidenspointner, R., Song, S., Caserta, C., Cho, Y. M., & Kory, N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.09.647991
Jia, H., Zhang, H., Liu, Y., Guo, J., Chen, W., Zhang, Y., Scarlat, M. M., Liu, L., & Hou, Z. (2025) · PLoS ONE · doi:10.1371/journal.pone.0324706
“Knockout of Nampt specifically in mouse muscle reduces the levels of NAD+ in the muscle, leading to muscle fiber degeneration and loss of physical functions resembling those of human type 2 diabetes, such as strength and endurance [47].”
Self-citationNAD+ metabolism as a target for anti-aging
Uchida, H., & Nakagawa, T. (2025) · Folia Pharmacologica Japonica · doi:10.1254/fpj.24072
Dong, G., Choi, J., Li, Y., Müller, D. C., Li, Z., Luo, Y. E., & RYAN, T. E. (2025) · Physiological Reports · doi:10.14814/phy2.70615
“For example, Frederick et al. (Frederick et al., 2016) demonstrated that NAD + depletion impairs muscle regeneration, and supplementation with NAD + precursors rescue satellite cell function and myofiber repair.”
InfluentialLai, X., Huang, S., Lin, S., Pu, L., Wang, Y., Lin, Y., Huang, W., & Wang, Z. (2022) · Figshare · doi:10.6084/m9.figshare.18132433
Song, M., Armenian, S. H., Bhandari, R., Lee, K., Ness, K. P. V., Putt, M., Lindenfeld, L., Manoukian, S., Wade, K., Dedio, A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20342385
Self-citationOthman, M. B., & Sakamoto, K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041912
“Additionally, NAMPT overexpression in skeletal muscle has been reported to boost exercise capacity and metabolic flexibility in obese mice, indicating tissue-specific functions of NAMPT in obesity treatment [15].”
Regulation of Aging by the Epigenome
Oyabu, M., & Kamei, Y. (2025) · KAGAKU TO SEIBUTSU · doi:10.1271/kagakutoseibutsu.63.123
Zhao, F., Zhao, Y., Cai, L., Wei, Y., & Wang, F. (2026) · Research Square · doi:10.21203/rs.3.rs-9058922/v1
Barbe, A. (2020) · theses.fr (ABES) · doi:10.70675/a1929a18zc99dz4f74zb8f8z614bf9e123e9
Cardoso, D. (2022) · theses.fr (ABES) · doi:10.70675/e5ce6d96z7253z4119zb119zc07f3977425d
Alambarrio, D. A., Li, X., Zedonek, S. S., Willis, S. E., Proctor, J. N., Mozafari, F., Call, J. A., Delgado, L. E., Doran, M. S., & Gonzalez, J. M. (2026) · Metabolites · doi:10.3390/metabo16040261
“Rapid NAD+ turnover or depletion is associated with reduced intracellular ATP availability [7].”
NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer
Li, L., Ma, Y., Pan, Y., Li, B. R., Chen, C. E., Wang, Q. L., Fu, Y., Fan, X. Q., Wang, S., & Wang, Z. (2026) · BMC Medicine · doi:10.1186/s12916-026-04986-7
“It is primarily derived from three pathways, with the salvage pathway contributing to over 85% of cellular NAD ⁺ production [27, 28].”
He, Q., Qin, W.-K., Yu, X., Jing, L., & Qi, Y. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1853301
From NAD+ metabolism to skeletal muscle function: The emerging role of ADP-ribosylation
Yonamine, C. Y., Espino-González, E., Lozano, S. P. A., & Treebak, J. T. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117866
Barjandi, G., Weidenfors, J. A., Schwieler, L., Erhardt, S., Jounger, S. L., & Ernberg, M. M. (2026) · PAIN Reports · doi:10.1097/pr9.0000000000001466
“11 Impaired NAMPT activity may also result in NAM accumulation through inefficient recycling.”
Strengthening muscle for healthy ageing: innovative treatments for sarcopenia
Ancel, S., Moal, E. L., Wang, Y. X., & Blau, H. M. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01514-3
An NAD+-responsive adipose signal coordinates inter-organ defense against muscle atrophy
Liang, N., He, J., Guo, X., Yan, J., Zhang, X., Peng, X., & Li, J. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.09.016
BindingDB (2025) · UC San Diego · doi:10.7270/q25x2fk7
Metadata
- Authors
- Frederick, D. W., Loro, E., Liu, L., Davila, A., Chellappa, K., Silverman, I. M., Quinn, W. J., Gosai, S. J., Tichy, E. D., Davis, J. G., Mourkioti, F., Gregory, B. D., Dellinger, R. W., Redpath, P., Migaud, M. E., Nakamaru-Ogiso, E., Rabinowitz, J. D., Khurana, T. S., & Baur, J. A.
- Affiliations
- University of Pennsylvania (US)
- Princeton University (US)
- ChromaDex (United States) (US)
- Queen's University Belfast (GB)
- Corresponding author
- Baur, Joseph A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 24
- Issue
- 2
- Pages
- 269-282
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4985182
- OpenAlex
- W2499764253
- Cited by
- 367
- References
- 39
- Citations by year
- 2026: 16 · 2025: 43 · 2024: 34 · 2023: 38 · 2022: 49 · 2021: 44 · 2020: 40 · 2019: 39 · 2018: 35 · 2017: 25 · 2016: 4
- FWCI
- 19.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/N001842/1)
- National Institute on Aging (R01AG043483)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK019525, R01DK098656)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR050950, P30AR069619)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- NAD+ homeostasis, skeletal muscle degeneration, visfatin, NAD+ salvage pathway, nicotinamide riboside, muscle fiber degeneration, muscle strength, exercise capacity, aging, muscle mass, NAD+ depletion, genotoxic stress
- MeSH terms
- Administration, Oral, Aging, Animals, Biological Availability, Energy Metabolism, Glucose, Homeostasis, Inflammation, Mice, Inbred C57BL, Mitochondria, NAD, Necrosis, Niacinamide, Organ Size, Physical Conditioning, Animal, Pyridinium Compounds, Transcription, Genetic, Mice, Knockout, Muscle, Skeletal, Muscle Strength, Nicotinamide Phosphoribosyltransferase
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