GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336838/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336838GEOGSEfalseEffect of NAMPT modulation in OIS-senescent IMR90 cells [invivo]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.2026/09/23GSE336838GSM9843560GSM9843561GSM9843562GSM9843563GSM9843564GSM9843565GSM9843566GSM9843567GSM9843600GSM9843568GSM9843601GSM9843569GSM9843571GSM9843572GSM9843573GSM9843530GSM9843574GSM9843531GSM9843575GSM9843576GSM9843532GSM9843533GSM9843577GSM9843534GSM9843578GSM9843579GSM9843535GSM9843536GSM9843537GSM9843538GSM9843539GSM9843570GSM9843582GSM9843583GSM9843584GSM9843540GSM9843541GSM9843585GSM9843542GSM9843586GSM9843587GSM9843543GSM9843544GSM9843588GSM9843545GSM9843589GSM9843546GSM9843547GSM9843548GSM9843549GSM9843580GSM9843581GSM9843593GSM9843550GSM9843594GSM9843551GSM9843595GSM9843596GSM9843552GSM9843553GSM9843597GSM9843554GSM9843598GSM9843599GSM9843555GSM9843556GSM9843557GSM9843558GSM9843559GSM9843590GSM9843591GSM984359234475336838Mus musculus[42620342]