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The effect of aging on gene expression of the African turquiose killfiish optic nerve

ABSTRACT: White matter dysfunction is a hallmark of brain aging and often precedes overt neurodegeneration, yet the cellular alterations connecting aging to white matter dysfunction remain poorly understood. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for ageing studies, displaying rapid ageing phenotypes within its four to six-month lifespan. Given the glia-dominant composition of the optic nerve, we reasoned that the killifish optic nerve would provide a suitable model to capture these age-related molecular signatures and gain insight into white matter aging. We therefore performed bulk RNAseq on optic nerves from young-adult (6-week-old) and aged (18-week-old) killifish. Our findings demonstrate that the aging killifish optic nerve reliably recapitulates the core molecular hallmarks of mammalian CNS aging. This conservation supports the use of the killifish optic nerve to resolve and understand how the CNS immune and glial cell populations contribute to these age-associated changes.

ORGANISM(S): Nothobranchius furzeri

PROVIDER: GSE347531 | GEO | 2026/09/23

REPOSITORIES: GEO

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Single-nucleus transcriptomic profiling identifies cell types and their age-associated transcriptional changes in the glia-rich optic nerve of the African turquoise killifish

Project description:White matter dysfunction is a hallmark of brain aging and often precedes overt neurodegeneration, yet the cellular alterations connecting aging to white matter dysfunction remain poorly understood. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for aging studies, displaying rapid aging phenotypes within its four to six-month lifespan. Previous transcriptomic profiling of the aging killifish retina suggested that CNS immune and glial cells undergo more pronounced age-associated transcriptomic changes than neurons. Given the heterogeneous responses of CNS immune and glial cells to aging, we performed snRNAseq on optic nerves from young-adult (6-week-old) and aged (18-week-old) killifish. Our findings demonstrate that all expected CNS immune and glial populations are present in the optic nerve and undergo distinct aging-associated transcriptional changes. Oligodendroglia, however, displayed the most pronounced alterations, including a marked induction of IFN-associated pathways and decrease in lipid metabolism, indicating that oligodendroglial are the major agign cell population.

2026-09-23 | GSE347881 | GEO

Effect of ageing on gene expression in the African turquiose killifish retina

Project description:The mammalian central nervous system (CNS) is susceptible to age-related pathologies, resulting in progressive, irreversible disease. Neurodegenerative eye conditions, like glaucoma and age-related macular degeneneration (AMD), are on the rise due to increased life expectancy. Despite this, there are currently no long-term therapies to prevent degeneration and vision loss. The short-lived African turquoise kililfsh (Nothobranchius furzeri GRZ-AD) is an ideal genetic model for ageing studies, exhibiting rapid ageing phenotypes within its four to six-mont lifespan. Investigating the molecular consequences of ageing in the retina, we conducted bulk RNA-sequencing, revealing dysregulation of genetic pathways associated with ageing CNS and retinal diseas in the aged killifish retina.

2024-08-27 | GSE255363 | GEO

The proteome of normal human sclera

Project description:The optic nerve is a white matter tract that conveys visual information to the brain. The sclera comprises the white, protective outer layer of the eye. A characterization of the proteome of normal human retrobulbar optic nerve and sclera may facilitate studies of the eye. We conducted a proteomic analysis of optic nerve and sclera from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 2,711 non-redundant proteins in retrobulbar optic nerve and 1945 non-redundant proteins in sclera. Optic nerve proteins included proteins expressed by oligodendrocytes (laminin, proteolipid protein, fibronectin), myelin proteins (myelin basic protein, myelin-associated glycoprotein), and paranodal structural proteins (ankyrin β, spectrin). Sclera included 18 collagen protein chains, small leucine-rich proteoglycans (decorin, biglycan, lumican, keratocan, prolargin, fibromodulin, mimecan), non-collagenous glycoproteins (fibronectin, vitronectin, laminin), extracellular matrix proteins (thrombospondins 1-4, dystroglycan, transgelins 1-3), and integrins alpha-V, alpha-1 and 2, beta-1, -2, and -5. Twenty-one unambiguous protein isoforms were identified in optic nerve and ten unambiguous protein isoforms were identified in sclera. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the optic nerve dataset identifier PXD001581.

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Oligodendroglial fatty acid metabolism as a central nervous system energy reserve

Project description:Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. Here, we addressed the question whether oligodendroglial lipid metabolism can provide an energy reserve in white matter tracts. Among other approaches including microscopy and electrophysiology applied to acutely isolated optic nerves from young adult mice used as a model system, we also employed quantitative proteome analysis to study alterations of the whole optic nerve proteome upon glucose deprivation. We compared optic nerve fractions from two different low-glucose incubation conditions (16 h in 0 mM glucose/10 mM sucrose or 24 h in 1 mM glucose/9 mM sucrose) with those from the respective control conditions in regular medium (10 mM glucose/0 mM sucrose). Optic nerve fractions from five animals per condition were processed with replicate digestion, resulting in two technical replicates per biological replicate and thus in a total of 20 LC-MS runs to be compared per individual experiment. We utilized a data-independent acquisition (DIA) workflow with alternating low and elevated energy (MSE) and an ion mobility-enhanced version thereof (referred to as UDMSE) to achieve both, a correct quantification of exceptionally abundant myelin proteins and a comprehensive coverage of the optic nerve proteome. Label-free protein quantification revealed a non-significant trend toward higher myelin protein abundance, a reduced abundance of some glycolytic enzymes, an increased abundance of fatty acid binding proteins and enzymes of fatty acid metabolism, as well as a higher steady-state level of some autophagy-related proteins. Taken together, our study indicates that ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism, and that the imbalance of myelin synthesis and degradation can underlie unexplained myelin thinning in aging and disease.

2024-07-16 | PXD053960 | Pride

Transcriptomic analyses of astrocyte heterogeneity within white matter tracts

Project description:Astrocytes are broadly categorized as protoplasmic or fibrous, with the former localized to synaptically dense gray matter regions and the latter associated with axons in the white matter. Much of what we know about astrocyte form and function is derived from the study of protoplasmic astrocytes, whereas fibrous astrocytes remain relatively unexplored. We investigated the transcriptome of uninjured fibrous astrocytes in the mouse from three regions: unmyelinated optic nerve head (ONH), myelinated optic nerve proper (ONP), and corpus callosum (CC).

2022-11-29 | GSE211515 | GEO

Identification of retinal cell types within the ageing African turquoise killifish retina and their respective age-related transcriptional changes using scRNA-seq

Project description:The mammalian central nervous system (CNS) and its retina are susceptible to age-related patholgoies, resulting in progressive, irreversible diseases like glaucoma and age-related macular degeneration (AMD), which are increasingly prevalent with rising life expectancy. Currently, there are no targeted long-term therapies to prevent vision loss. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for ageing studies, displaying rapid ageing phenotypes within its four to six-month lifespan. Our investigation on the molecular consequences of ageing in the retina, employing scRNA-sequencing, shows a a comprehensive overview of the cellular heterogeneity of the killifish retina, uncovering age-related gene expression changes specific to certain retinal cell populations.

2024-08-21 | GSE255364 | GEO

small RNA-seq of three tissues (brain, liver, skin) of Nothobranchius furzeri (at different ages) and Brain samples of 6 other killifish species

Project description:The RNA-seq data contain 3 tissues (brain, liver, skin) of N. furzeri strains MZM-0410 and GRZ plus 2 biological replicates of brain of 6 other killifish species. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)

2017-09-29 | GSE104321 | GEO

The proteome of human retrobulbar optic nerve

Project description:The optic nerve is a white matter tract that conveys visual information to the brain. A detailed investigation of the proteome of the normal human retrobulbar optic nerve may help facilitate studies of the biology and pathophysiology of the optic nerve. We conducted an in-depth proteomic analysis of optic nerve from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 2,711 non-redundant proteins in the human retrobulbar optic nerve, including the astrocytic marker glial fibrillary acidic protein, several proteins expressed by oligodendrocytes (laminin, proteolipid protein, and fibronectin), myelin proteins (myelin basic protein, myelin-associated glycoprotein), paranodal structural proteins (neurofascin, contactin, α, β, and γ adducins, septin 2, endophilin, ankyrin β, spectrin), proteins involved in neuronal protection and regeneration (α crytallins A and B, dedicator of cytokinesis proteins, ciliary neurotrophic factor), proteins associated with open-angle glaucoma (thioredoxin, heat shock protein-70), and proteins associated with optic neuritis (aquaporin-4). Twenty-one unambiguous protein isoforms were identified in the optic nerve.

2016-08-24 | PXD001581 | Pride

Regulation of PERK-eIF2Î± Signaling by Tuberous Sclerosis Complex-1 Controls Homeostasis and Survival of Myelinating Oligodendrocytes

Project description:Tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by mutations in either TSC1 or TSC2, exhibits white matter abnormalities including CNS myelin deficits. however, underlying mechanisms are not fully understood. Here we find that, unexpectedly, constitutive activation of mTOR signaling caused by Tsc1 deletion in the oligodendrocyte lineage results in severe myelination defects and oligodendrocyte cell death. Expression profiling analysis reveals that Tsc1 ablation induces prominent endoplasmic reticulum (ER) stress responses through the PERKâeIF2Î± dependent signaling axis and activates Fas-JNK apoptotic pathways. Our studies suggest that TSC1-mTOR signaling acts as an important checkpoint for maintaining oligodendrocyte homeostasis. Gene expression profiling of optic nerve from P12 control and Tsc1cKO mice

2016-07-22 | E-GEOD-74893 | biostudies-arrayexpress

Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis - ON snRNA-seq data

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