Healthy aging and muscle function are positively associated with NAD+ abundance in humans
Open accessAbstract
Skeletal muscle is greatly affected by aging, resulting in a loss of metabolic and physical function. However, the underlying molecular processes and how (lack of) physical activity is involved in age-related metabolic decline in muscle function in humans is largely unknown. Here, we compared, in a cross-sectional study, the muscle metabolome from young to older adults, whereby the older adults were exercise trained, had normal physical activity levels or were physically impaired. Nicotinamide adenine dinucleotide (NAD+) was one of the most prominent metabolites that was lower in older adults, in line with preclinical models. This lower level was even more pronounced in impaired older individuals, and conversely, exercise-trained older individuals had NAD+ levels that were more similar to those found in younger individuals. NAD+ abundance positively correlated with average number of steps per day and mitochondrial and muscle functioning. Our work suggests that a clear association exists between NAD+ and health status in human aging.
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Mitochondrial dysfunction and low NAD+ levels are hallmarks of skeletal muscle ageing and sarcopenia.
“Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1–3”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [2]
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Zheng, M., Schultz, M. B., & Sinclair, D. A. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.02.001 · Cited by 62 · see citing works
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59 · see citing works
Yaku, K., Palikhe, S., Iqbal, T., Hayat, F., Watanabe, Y., Fujisaka, S., Izumi, H., Yoshida, T., Karim, M., Uchida, H., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr1538 · Cited by 40 · see citing works
“The skeletal muscle is considered an important target organ for NAD + replenishment therapy ( 34 – 36 ).”
- Authors
- Janssens, G. E., Grevendonk, L., Perez, R. Z., Schomakers, B. V., de Vogel-van den Bosch, J., Geurts, J. M. W., van Weeghel, M., Schrauwen, P., Houtkooper, R. H., & Hoeks, J.
- Affiliations
- Amsterdam University Medical Centers (NL)
- Maastricht University (NL)
- FrieslandCampina (Netherlands) (NL)
- Corresponding author
- Houtkooper, Riekelt H.
- ORCID
- Venue
- Nature Aging
- Published
- 2022-02-17
- Volume
- 2
- Issue
- 3
- Pages
- 254-263
- ISSN
- 2662-8465 (ISSN-L)
- OpenAlex
- W4213292045
- Cited by
- 103
- References
- 80
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 27 · 2023: 22 · 2022: 12
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Velux Stiftung
- European Commission (840110, HORIZON2020)
- ZonMw (91715305)
- H2020 European Research Council (638290)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- NAD+, healthy aging, skeletal muscle, muscle metabolome, exercise training, physical activity, mitochondrial function, muscle function, older adults, physical impairment, step count, age-related metabolic decline
- MeSH terms
- Healthy Aging, Aged, Aging, Cross-Sectional Studies, Humans, NAD, Muscle, Skeletal
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