{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336838/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336838"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Effect of NAMPT modulation in OIS-senescent IMR90 cells [invivo]","description":"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. 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. 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.","dates":{"publication":"2026/09/23"},"accession":"GSE336838","cross_references":{"GSM":["GSM9843560","GSM9843561","GSM9843562","GSM9843563","GSM9843564","GSM9843565","GSM9843566","GSM9843567","GSM9843600","GSM9843568","GSM9843601","GSM9843569","GSM9843571","GSM9843572","GSM9843573","GSM9843530","GSM9843574","GSM9843531","GSM9843575","GSM9843576","GSM9843532","GSM9843533","GSM9843577","GSM9843534","GSM9843578","GSM9843579","GSM9843535","GSM9843536","GSM9843537","GSM9843538","GSM9843539","GSM9843570","GSM9843582","GSM9843583","GSM9843584","GSM9843540","GSM9843541","GSM9843585","GSM9843542","GSM9843586","GSM9843587","GSM9843543","GSM9843544","GSM9843588","GSM9843545","GSM9843589","GSM9843546","GSM9843547","GSM9843548","GSM9843549","GSM9843580","GSM9843581","GSM9843593","GSM9843550","GSM9843594","GSM9843551","GSM9843595","GSM9843596","GSM9843552","GSM9843553","GSM9843597","GSM9843554","GSM9843598","GSM9843599","GSM9843555","GSM9843556","GSM9843557","GSM9843558","GSM9843559","GSM9843590","GSM9843591","GSM9843592"],"GPL":["34475"],"GSE":["336838"],"taxon":["Mus musculus"],"PMID":["[42620342]"]}}