Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883499 | ENA |
REPOSITORIES: ENA
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: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: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+ 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: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
Project description:NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling
| PRJNA911143 | ENA
Project description:Hearing mediates many behaviors critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviors for survival to old age; however relatively little is known about the aging bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and aging bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear aging, with similar hair cell counts, afferent, and efferent innervation patterns in young and aging bats. Here we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.
2024-09-30 | GSE274777 | GEO