Cited by 501Sirtuins and Resveratrol in MedicineBiochemical and Molecular ResearchGenetics, Aging, and Longevity in Model Organisms

NAD(+) in aging: molecular mechanisms and translational implications

Open access
Fang, Evandro F., Lautrup, Sofie, Hou, Yujun, Demarest, Tyler G., Croteau, Deborah L., Mattson, Mark P., Bohr, Vilhelm A.·2017·Trends in Molecular Medicine

Abstract

The coenzyme NAD+ is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD+ levels is important for cells with high energy demands and for proficient neuronal function. NAD+ depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD+ decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD+ levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD+ biosynthesis, together with putative mechanisms of NAD+ action against aging, including recent preclinical and clinical trials.

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Crossref · 10.1016/j.molmed.2017.08.001

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  • NAD+ is a vital redox cofactor for metabolism and ATP production and a key substrate for at least four enzyme families involved in healthspan and longevity.

    “NAD+ is a vital redox cofactor for metabolism and ATP production, and a key substrate for at least four families of enzymes involved in healthspan and longevity (Fang et al., 2017; Gomes et al., 2013; Verdin, 2015).”

    From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Fang et al., 2017

  • SIRTs, PARPs, CD38/CD157, and SARM1 compete for cellular NAD+, so hyperactivation of one enzyme can impair other NAD+-dependent enzymes.

    “SIRTS, PARPs, CD38/CD157, and SARM1 compete with each other to consume cellular NAD+; thus, the hyperactivation of one enzyme can impair the activities of other NAD+-dependent enzymes.”

    From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Fang et al., 2017

  • Age-related NAD+ depletion is positively related to the 10 hallmarks of brain aging.

    “Emerging findings are revealing linkages by which age-related NAD+ depletion is positively related to the 10 hallmarks of brain aging.”

    From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Fang et al., 2017

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Authors
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A.
Affiliations
  • National Institutes of Health (US)
  • University of Copenhagen (DK)
Corresponding author
Bohr, Vilhelm A.
Venue
Trends in Molecular Medicine
Publisher
Elsevier BV
Published
2017-10
Volume
23
Issue
10
Pages
899-916
ISSN
1471-4914 (ISSN-L)
OpenAlex
W2751352835
Cited by
501
References
119
Citations by year
2026: 42 · 2025: 75 · 2024: 69 · 2023: 45 · 2022: 64 · 2021: 74 · 2020: 53 · 2019: 48 · 2018: 29 · 2017: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Locations
  • Trends in Molecular Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Scopus (Elsevier) (submittedVersion)
Funders
  • Intramural Research Program of the National Institute on Aging (2015-2016, 2016-2017)
  • The Oticon Foundation
  • Ib Henriksen’s Foundation
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
NAD+, aging, NAD+ depletion, NAD biosynthesis, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, cardiovascular disease, muscle atrophy, age-related diseases, NAD+ supplementation, cellular bioenergetics, stress response
MeSH terms
Aging, Alzheimer Disease, Animals, Cardiovascular Diseases, Energy Metabolism, Humans, Muscular Atrophy, NAD, Parkinson Disease

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