Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883499 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21679459_1.fastq.gz | Fastqsanger.gz | |||
| SRR21679459_2.fastq.gz | Fastqsanger.gz | |||
| SRR21679460_1.fastq.gz | Fastqsanger.gz | |||
| SRR21679460_2.fastq.gz | Fastqsanger.gz | |||
| SRR21679461_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Age-related hearing loss (ARHL) is the most common sensory disabling condition associated with aging in humans. Yet, there are still no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe treatment approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well-tolerated even for long-term use and is already shown effective in various disease models including Alzheimer’s and Parkinson’s Disease. However, its beneficial impact on ARHL is not known. In this study, we investigated transcriptomic profile in the cochlea of the mice (mtKeima strain) that are treated with NR for 10 months vs. non-treated.
2023-09-20 | GSE213994 | GEO
Project description:Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
| S-EPMC10497810 | biostudies-literature
Project description:Age-related hearing loss (ARHL) is one of the most common disorders affecting elderly individuals. There is an urgent need for effective preventive measures for ARHL because none are currently available. Cockayne syndrome (CS) is a premature aging disease that presents with progressive hearing loss at a young age, but is otherwise similar to ARHL. There are two human genetic complementation groups of CS, A and B. While the clinical phenotypes in patients are similar, the proteins have very diverse functions, and insight into their convergence is of great interest. Here, we use mouse models for CS (CSA -/- and CSB m/m ) that recapitulate the hearing loss in human CS patients. We previously showed that NAD+, a key metabolite with various essential functions, is reduced in CS and associated with multiple CS phenotypes. In this study, we report that NAD+ levels are reduced in the cochlea of CSB m/m mice and that short-term treatment (10 days) with the NAD+ precursor nicotinamide riboside (NR), prevents hearing loss, restores outer hair cell loss, and improves cochlear health in CSB m/m mice. Similar, but more modest effects were observed in CSA -/- mice. Remarkably, we observed a reduction in synaptic ribbon counts in the presynaptic zones of inner hair cells in both CSA -/- and CSB m/m mice, pointing to a converging mechanism for cochlear defects in CS. Ribbon synapses facilitate rapid and sustained synaptic transmission over long periods of time. Ribeye, a core protein of synaptic ribbons, possesses an NAD(H) binding pocket which regulates its activity. Intriguingly, NAD+ supplementation rescues reduced synaptic ribbon formation in both CSA -/- and CSB m/m mutant cochleae. These findings provide valuable insight into the mechanism of CS- and ARHL-associated hearing loss, and suggest a possible intervention.
| S-EPMC6946667 | biostudies-literature
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
Project description:NAD+ levels decline with age and in certain disease conditions. NAD+ precursors have been shown to stimulate NAD+ biosynthesis and ameliorate various age-associated diseases in mouse models. However, NAD+ metabolism is complicated in cancer and its role in triple-negative breast cancer (TNBC) remains elusive. Here, we show that NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model. Sirtuin1 lysine deacetylase (SIRT1) is required for the effects since SIRT1 knockdown blocks NAD+-suppressed tumor metastasis. Overexpression of SIRT1 effectively impairs the metastatic potential of TNBC. Importantly, the interaction between SIRT1 and p66Shc causes the deacetylation and functional inactivation of p66Shc, which inhibits epithelial-mesenchymal transition (EMT). Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.
2023-01-23 | GSE220683 | GEO
Project description:Regular exercise significantly slowed age-related hearing loss (AHL) and cochlear degeneration in a well- established murine model.
2017-02-08 | GSE84682 | 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:Lactobacillus paracasei Supplementation Prevents Early-Life Stress Induced anxiety-like behaviour in adolescent rats
| PRJEB45530 | ENA
Project description:NAD+ supplementation normalizes neuroinflammation and senescence via the cGAS-STING pathway
| PRJNA560913 | ENA
Project description:Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confrimed that severe age-related hearing loss occured in 36-week-old mice, whereas moderate hearing loss occured in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealeed that 15 mitochondrial process categories, including â??mitochondrial electron transport chainâ??, â??oxidative phosphorylationâ??, â??respiratory chain complex Iâ??, â??respiratory chain complex IVâ??, and â??respiratory chain complex Vâ??, were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Experiment Overall Design: To determine the effects of age-related hearing loss, each 7-week-old sample (n = 3) was compared to each 36-week-old sample (n = 3), generating a total of nine pairwise comparisons. Using DAVIS and EASE, the identified genes were assign to â??GO: Biological Processâ?? categories of Gene Ontology Consortium. Furthermore, we used EASE to determine the total number of genes that were assigned to each biological process category, and to perform Fisher exact test. Quality control measures were not used. No replicates were done. Dye swap was not used.
2008-06-14 | E-GEOD-6045 | biostudies-arrayexpress