Why NAD + Declines during Aging: It’s Destroyed
Open accessAbstract
NAD(+) is required not only for life but for a long life. In this issue, Camacho-Pereira et al. (2016) implicate CD38 in the decline of NAD(+) during aging, with implications for combating age-related diseases.
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Senescent cells can decrease NAD+ via SASP activation of CD38 on macrophages, and senolytics partially restore tissue NAD+ levels.
“Senescent cells can decrease NAD+ through SASP activation of the NAD-degrading enzyme CD38 on the surface of macrophages and, remarkably, senolytics partially restore tissue NAD+ levels139,140.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [140]
The paper’s Abstract links rising CD38 activity during aging to declining NAD+ levels and reports that mice lacking CD38 retain higher NAD+ levels. It does not describe SASP activation of CD38 on macrophages or report that senolytics restore tissue NAD+; its discussion of inflammation as a possible trigger is speculative. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSirtuin activity and NAD levels both decline with age.
“Sirtuin activity and NAD levels both decline with age116,117.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [117]
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- Authors
- Schultz, M. B., & Sinclair, D. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sinclair, David A.
- ORCID
- Sinclair, David A.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 965-966
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5088772
- OpenAlex
- W2423823537
- Cited by
- 126
- References
- 10
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 14 · 2023: 14 · 2022: 22 · 2021: 25 · 2020: 16 · 2019: 12 · 2018: 6 · 2017: 3 · 2016: 1
- FWCI
- 4.21
- 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)
- Funders
- National Institute on Aging (R37AG028730)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100263)
- 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
- aging, CD38, NAD+ metabolism, age-related diseases, sirtuins, NAD+ salvage pathway
- MeSH terms
- Aging, Animals, Mitochondria, Models, Biological, NAD, Mice, ADP-ribosyl Cyclase 1
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