NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle
Open accessAbstract
Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like deposits and mitochondrial dysfunction during natural aging in the body wall muscle of C. elegans , in human primary myotubes, and in mouse skeletal muscle, partially phenocopying inclusion body myositis (IBM). Importantly, NAD + homeostasis is critical to control age-associated muscle amyloidosis. Treatment of either aged N2 worms, a nematode model of amyloid-beta muscle proteotoxicity, human aged myotubes, or old mice with the NAD + boosters nicotinamide riboside (NR) and olaparib (AZD) increases mitochondrial function and muscle homeostasis while attenuating amyloid accumulation. Hence, our data reveal that age-related amyloidosis is a contributing factor to mitochondrial dysfunction and that both are features of the aging muscle that can be ameliorated by NAD + metabolism-enhancing approaches, warranting further clinical studies.
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Pharmacological increases in NAD+ have been shown to restore mitochondrial function in various preclinical models of aging.
“Pharmacological increases in NAD + has been shown to restore mitochondrial function in various preclinical models of aging [174].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [174]
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- Authors
- Romani, M., Sorrentino, V., Oh, C.-M., Li, H., de Lima, T. I., Zhang, H., Shong, M., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Gwangju Institute of Science and Technology (KR)
- Chungnam National University (KR)
- Corresponding author
- Auwerx, Johan
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 34
- Issue
- 3
- Pages
- 108660
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7816122
- OpenAlex
- W3123062723
- Cited by
- 92
- References
- 59
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 13 · 2023: 22 · 2022: 19 · 2021: 7 · 2020: 2
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- National University of Singapore (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2019/11171-7)
- Ministry of Education (2016R1A6A3A04010466)
- Stiftung für die Erforschung der Muskelkrankheiten
- National Research Foundation of Korea
- European Research Council (ERC-AdG-787702)
- China Scholarship Council
- Hospices Civils de Lyon
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_160318, 31003A_179435, GRL 2017K1A1A2013124)
- École Polytechnique Fédérale de Lausanne
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- muscle aging, amyloidosis, mitochondrial dysfunction, proteostasis, inclusion body myositis, nicotinamide riboside, olaparib, skeletal muscle, amyloid-beta, proteotoxicity, NAD+ metabolism, myotubes
- MeSH terms
- Aging, Amyloidosis, Animals, Homeostasis, Humans, NAD, Caenorhabditis elegans, Muscle, Skeletal, Mice
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