The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline
Open accessAbstract
Tissue nicotinamide adenine dinucleotide (NAD+) decline has been implicated in aging. We have recently identified CD38 as a central regulator involved in tissue NAD+ decline during the aging process. CD38 is an ecto-enzyme highly expressed in endothelial and inflammatory cells. To date, the mechanisms that regulate CD38 expression in aging tissues characterized by the presence of senescent cells is not completely understood. Cellular senescence has been described as a hallmark of the aging process and these cells are known to secrete several factors including cytokines and chemokines through their senescent associated secretory phenotype (SASP). Here we investigated if the cellular senescence phenotype is involved in the regulation of CD38 expression and its NADase activity. We observed that senescent cells do not have high expression of CD38. However, the SASP factors secreted by senescent cells induced CD38 mRNA and protein expression and increased CD38-NADase activity in non-senescent cells such as endothelial cells or bone marrow derived macrophages. Our data suggest a link between cellular senescence and NAD+ decline in which SASP-mediated upregulation of CD38 can disrupt cellular NAD+ homeostasis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Senescent cells and their SASP activate CD38 expression and promote CD38-dependent NADase activity in macrophages.
“another group has also independently shown that senescent cells and their SASP activate CD38 expression and promote CD38-dependent NADase activity in macrophages105,106.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [106]
CD38-overexpressing M1-like macrophages are activated directly by inflammatory cytokines secreted by senescent cells.
“these CD38-overexpressing M1-like macrophages are activated directly by inflammatory cytokines secreted by senescent cells (discussed in more detail later)45,105,106”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [106]
CD38 is emerging as a key enzyme involved in inflammageing and senescence, which are strongly associated with neurodegenerative diseases.
“CD38 is emerging as a key enzyme involved in inflammageing and senescence45,105,106, which are strongly associated with neurodegenerative diseases124,128,168,169.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [106]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 38 · Cited by 138
Research works printed but not linked: 1
- [32]Jablonski KA, Amici SA, Webb LM, Ruiz-Rosado JdD, Popovich PG, Partida-Sanchez S, et al. (2015) Novel Markers to Delineate Murine M1 and M2 Macrophages. PLoS ONE 10(12): e0145342. 26699615 PMC4689374
- Authors
- Chini, C., Hogan, K. A., Warner, G. M., Tarragó, M. G., Peclat, T. R., Tchkonia, T., Kirkland, J. L., & Chini, E.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Chini, Eduardo
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 513
- Issue
- 2
- Pages
- 486-493
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC6486859
- OpenAlex
- W2936767994
- Cited by
- 138
- References
- 38
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 14 · 2023: 14 · 2022: 24 · 2021: 20 · 2020: 21 · 2019: 9
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (AG-26094, AG-58812)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- CD38, NADase activity, cellular senescence, senescence-associated secretory phenotype, aging, endothelial cells, bone marrow-derived macrophages, NAD+ homeostasis
- MeSH terms
- Aging, Animals, Cells, Cultured, Female, Humans, Macrophages, Mice, Inbred C57BL, Middle Aged, NAD, Cellular Senescence, Endothelial Cells, ADP-ribosyl Cyclase 1, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
