Omics · study · 2026
Effect of NAMPT modulation in OIS-senescent IMR90 cells [invivo]
Listed in NCBI GEO
Nicotinamide adenine dinucleotide (NAD+) metabolism becomes dysregulated with age and has emerged as a targetable feature of aging and age-related dysfunction, yet the cellular contexts in which altered NAD+ homeostasis creates therapeutic vulnerabilities remain incompletely defined.
Description
Here, we identify senescence as one such context. Senescent cells retained elevated levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAM salvage pathway yet exhibited a paradoxical reduction in NAD+ turnover, suggesting a disconnect between protein abundance and enzymatic output.
In mice, SBI-0802162 reduced circulating nicotinamide (NAM), revealing a limitation of sustained NAM salvage pathway activation and prompting the development of a combination strategy with dietary NAM supplementation. Co-administration of SBI-0802162 and NAM robustly increased tissue NAD+, suppressed select age-associated inflammatory signatures in a tissue-specific manner and preserved physical performance of aged mice.
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These effects occurred alongside reductions in food intake and body weight, which were observed whether SBI-0802162 and NAM were administered voluntary in the diet or by oral gavage. Together, these findings identify elevated NAMPT coupled with reduced NAD+ turnover as a metabolic vulnerability in senescent cells and support combined NAMPT activation with dietary NAM as a novel strategy to restore NAD+ homeostasis and improve age-associated inflammation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336838 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336838 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1483440 ncbi.nlm.nih.gov/bioproject/PRJNA1483440 ↗
project · from NCBI GEO
- PubMed 42620342 pubmed.ncbi.nlm.nih.gov/42620342 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE336838 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |