Ion-coupled Transfersome Complexes for Enhanced Transdermal NAD+ Repletion and Defense Against Cellular Senescence Signatures
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282453 | GEO | 2025/11/20
REPOSITORIES: GEO
Similar Datasets
Project description:Ion-coupled Transfersome Complexes for Enhanced Transdermal NAD+ Repletion and Defense Against Cellular Senescence Signatures
| PRJNA1188606 | ENA
Project description:Metabolic dysfunction is a primary feature of the premature aging Werner syndrome (WS), a heritable human disease caused by mutations in the gene encoding the DNA helicase Werner (WRN). However, the relationship between WRN mutation and its severe metabolic phenotypes is unclear. Here we report mitochondrial dysfunction and depletion of NAD+, a fundamental ubiquitous cofactor, in WS patient samples and WS animal models. NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably delays accelerated aging, including stem cell dysfunction in both C. elegans and Drosophila models of WS. Mechanistically, WRN physically binds to a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) and facilitates its NAD+ production. Our findings reveal an unprecedented anti-aging mechanism of WRN that integrates its new function of NAD+ synthesis to coordinate mitochondrial maintenance and energy expenditure, and suggest therapeutic potential.
2019-08-16 | GSE108968 | GEO
Project description:Left ventricular (LV) diastolic dysfunction is a hallmark of Heart Failure with preserved Ejection Fraction (HFpEF), an escalating global health challenge. We demonstrated selective depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) and the rate-limiting enzyme of the NAD+ biosynthetic salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), in human myocardium with LV diastolic dysfunction. We showed that NAD+ can be replenished in human myocardium with diastolic impairment ex vivo, despite reduced NAMPT expression. In a murine model of HFpEF [a combination exposure to high-fat diet (HFD) and L-NG-Nitro arginine methyl ester (L-NAME)], we compared the benefits of NAD+ precursor supplementation versus dietary intervention. We tested NAD+ repletion by nicotinamide riboside (NR) supplementation using two clinically-relevant strategies: 1) Prophylactic NR repletion before HFpEF onset, and 2) Therapeutic NR repletion after the development of HFpEF. We found that dietary intervention (replacement of HFD and L-NAME with healthy diet) restored myocardial insulin-dependent glucose uptake and glycolysis but did not rescue HFpEF. In contrast, both NAD+ repletion strategies prevented or rescued HFpEF, respectively, plausibly due to restoration of myocardial iron homeostasis, recoupling of glycolysis to the TCA cycle, and upregulation of antioxidant defense.
2024-08-09 | PXD033027 | Pride
Project description:To gain deeper insights into antibacterial mechanisms of NAD+ and bacterial adaptation, we generated and sequenced NAD+ resistant clones of Spn. For this purpose, Spn was cultivated in liquid medium with increasing concentrations (50 µM to 5 mM) of NAD+. After six passages, bacteria were plated on blood agar supplemented with 500 µM NAD+ and three clones were picked
2023-06-11 | E-MTAB-12644 | biostudies-arrayexpress
Project description: Not available
| S-EPMC10070388 | biostudies-literature
Project description:We developed a Copper-free, strain-promoted azide-alkyne cycloaddition reaction (SPAAC) to capture NAD-RNAs without RNA degradation. We examined the specificity of CuAAC and SPAAC reactions towards NAD+ vs. m7G, and found that both prefer NAD+ but also act on m7G. We show that m7G-capped RNA can be immuno-depleted, allowing for the specific identification of NAD-RNA via the SPAAC reaction and sequencing, which we name SPAAC-NAD-seq. Subjecting Arabidopsis RNA to both the original NAD captureSeq and SPAAC-NAD-seq, we found that more NAD+-capped RNA was identified by the latter, particularly those with low abundance. This led to the discovery of new gene ontology terms such as starch biosynthsis, intracellular protein transport and response to cadmium stress associated with genes that produce NAD-RNA. Furthermore, reads were uniformly distributed along gene bodies, which suggested that SPAAC-NAD-seq retained full-length sequence information. SPAAC-NAD-seq enables specific and efficient discovery of NAD-RNA in prokaryotes, and when combined with m7G-RNA depletion, in eukaryotes.
2021-04-14 | GSE162114 | GEO
Project description:Analysis of treatment at gene expression level in aged mice. Results provide important information of the response of drug modifying NAD metabolism which has been implicated in anti-aging effect of calorie restriction in aging process. Total RNA obtained from skeletal muscles and brain (cortex) subjected to calorie restriction or β-lapachone treatment compared to untreated control.
2011-05-01 | E-GEOD-23218 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7063679 | biostudies-literature
Project description:Background: Sarcopenia contributes to all-cause mortality in the elderly; however, there is no specific treatment. Mesenchymal stromal cells (MSCs) ameliorate age-related muscle loss and dysfunction, and are potential therapeutic candidates for sarcopenia. However, their activity is easily affected by the surrounding environment and they are prone to replicative senescence during in vitro culture. Therefore, a drug that delays aging and enhances its function is required. Here, we investigated whether nicotinamide adenine dinucleotide (NAD+) pretreatment enhances the therapeutic efficacy of MSCs on skeletal muscle atrophy and its underlying mechanism in a D-gal-induced aging model. Methods: C57BL/6J mice and C2C12-differentiated myotubes exposed to D-gal were used to explore the effects of MSCs/NAD+-MSCs on muscle atrophy. MSCs/NAD+-MSCs were injected into the skeletal muscles of the hind limbs every 7 days for six cycles. Treadmill running and grip strength tests were used to evaluate the muscle strength. Muscle weight and fiber cross-sectional area (CSA) were used to measure muscle mass. Multiomics analysis of quadriceps and NAD+-pretreated MSCs (NAD+-MSCs), western blotting of muscle atrophy signaling, including Atrogin 1 and MuRF1, the mitochondrial complex, fatty acid oxidation indicators, and Seahorse analysis were performed to explore the underlying mechanisms. Results: MSCs increased grip strength (p=0.0005), running endurance (p=0.0006), and muscle mass (p=0.0165 for tibialis anterior (TA) muscle, p=0.0049 for soleus (SO) muscle) in D-gal-treated mice, with elevated muscle fiber CSA (p<0.0001), and reduced Atrogin1 (p=0.0242) and MuRF1 expression (p=0.0009). NAD+ pretreatment increased the effect of MSCs on muscle atrophy (p=0.0009 for grip strength, p=0.0169 for running endurance, p=0.0506 for TA muscle weight, p=0.0238 for SO muscle weight, p=0.0002 for muscle fiber CSA, p=0.0005 for Atrogin1 expression and p=0.0223 for MuRF1 expression). MSCs/NAD+-MSCs activated the SIRT1/PGC-1α signaling, enhanced mitochondrial function and fatty acid oxidation in D-gal-induced mice and C2C12 myotubes. SIRT1 knockdown weakened the beneficial effects of MSCs/NAD+-MSCs on muscle atrophy. RNA-seq of MSCs/NAD+-MSCs and proteomic analysis of their supernatants revealed that NAD+ enhanced the therapeutic effect of MSCs by promoting NAMPT secretion. Conclusions: NAD+ enhances the therapeutic effect of MSCs on age-related muscle atrophy by promoting NAMPT secretion, which acts on the SIRT1 signaling pathway, and improves mitochondrial function and fatty acid oxidation in skeletal muscles. This study provides new insights and a theoretical basis for the clinical treatment of sarcopenia.
2025-12-17 | GSE304351 | GEO
Project description:Raw data of NAD captureSeq of total RNA isolated from exponential and stationary phase M. smegmatis cultures.
2024-12-31 | E-MTAB-10246 | biostudies-arrayexpress