Data files for manuscript "NAD+ flux is maintained in aged mice"
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Joseph A. Baur
PROVIDER: MSV000087933 | MassIVE | Mon Aug 02 20:15:00 BST 2021
REPOSITORIES: MassIVE
Similar Datasets
Project description:NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass, despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function. Messenger RNA was isolated from quadriceps muscle of mice from three different age groups and three different genotypes. Wildtype mice were aged 4, 7, and 24 months. Mice deficient for Nampt in skeletal muscle (mNKO) were aged 7 months. Mice overexpressing Nampt in skeletal muscle were aged 4 and 24 months.
2016-07-22 | E-GEOD-74570 | biostudies-arrayexpress
Project description:The coenzyme NAD is consumed by signalling enzymes such as poly-ADP-ribose-polymerases (PARPs) and sirtuins. Understanding the mechanisms of aging-associated NAD decline and how cells cope with decreased NAD concentrations requires model systems reflecting chronic NAD deficiency. To evoke compartment-specific over-consumption of NAD, we have engineered cell lines expressing PARP activity in mitochondria, the cytosol, endoplasmic reticulum, and peroxisomes. Additionally, we have engineered cell lines that lack a functional gene for the human mitochondrial transporter SLC25A51 and the NAD biosynthesis enzyme NMNAT3. Isotope-tracer flux measurements and mathematical modelling showed that the lowered NAD concentration limits total NAD consumption kinetically. Moreover, NAD biosynthesis rate and capacity remained unchanged, thereby also precluding an increase of total NAD turnover. The chronic NAD deficiency was surprisingly well tolerated unless the mitochondria were targeted. Oxidative phosphorylation and glycolysis were little affected by NAD over-consumption in the other compartments. Likewise, peroxisomal NAD over-consumption was balanced by mitochondrial NAD decrease to maintain beta-oxidation of very long chain fatty acids in peroxisomes. We propose that subcellular NAD pools are interconnected, with mitochondria acting as a rheostat to facilitate NAD-dependent processes in organelles with excessive consumption.
2024-02-07 | GSE255209 | GEO
Project description:Aging is accompanied by a decline in neovascularisation potential and increased susceptibility to ischemic injury. Here, we confirm the age-related impaired neovascularization following ischemic leg injury and impaired angiogenesis. The age-related deficits in angiogenesis arose primarily from diminished EC proliferation capacity, but not migration or VEGF sensitivity. Aged EC harvested from the mouse hindlimb displayed a pro-angiogenic gene expression phenotype, along with considerable changes in metabolic genes. Metabolomics analysis and 13C glucose tracing revealed that late passage HUVECs display impaired ATP production and altered glycolysis and TCA cycle intermediates, with significant shifts occurring at nicotinamide adenine dinucleotide (NAD⁺)-dependent steps along with NAD+ depletion, suggestive of compromised NAD⁺ metabolism. Supplementation with nicotinamide mononucleotide (NMN), a precursor of NAD⁺, enhances enhanced late-passage EC proliferation and sprouting angiogenesis from aged mice aortas. Taken together, our study illustrates the centrality of NAD+-dependent metabolism in the maintenance of EC proliferation capacity with age.
2024-11-25 | GSE270697 | GEO
Project description:NAD+is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.
2019-08-29 | GSE133261 | GEO
Project description:NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass, despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function.
2016-07-22 | GSE74570 | GEO
Project description:These are the raw mass spec data files for manuscript "NAD precursors cycle between host tissues and the gut microbiome", Karthikeyani Chellappa et al. Check out "Mass Spec data_KEY_Chellappa et al Cell Metabolism_2022.xlsx" for data file arrangement.
2022-10-06 | MSV000090481 | MassIVE
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: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: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:NAD+ supplementation has been shown to impart significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevated NAD+ has been shown to improve the function of some adult stem cells, with implications that these changes could lead to sustained improvement of the tissue or system. We examined the effect of elevating NAD+ levels in models with reduced hematopoietic stem cell (HSC) potential (ATM-deficient and aged mice) and show that supplementation of NR, a NAD+ precursor, leads to improved lymphoid lineage potential and long-term cell-autonomous benefits. Transcriptional profiles from HSCs show changes driven by NR repress myeloid gene signatures, which may lead to the increased lymphoid output. Our work characterizes the improved lymphoid-potential from short-term NR treatment in functionally compromised HSCs and highlights potentially detrimental aspects of supplementing NAD+ to proficient systems.
2021-09-14 | GSE147662 | GEO