A novel immune modulator IM33 mediates a glia-microbiota-neuronal axis that controls lifespan
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA768826 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16206862_1.fastq.gz | Fastqsanger.gz | |||
| SRR16206862_2.fastq.gz | Fastqsanger.gz | |||
| SRR16206863_1.fastq.gz | Fastqsanger.gz | |||
| SRR16206863_2.fastq.gz | Fastqsanger.gz | |||
| SRR16206864_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Using Drosophila we identified a glia-secreted antimicrobial peptide IM33, which alters gut microbiota to modulate sleep. To understand how the gut commensal Lactiplantibacillus plantarum functions in the brain to regulate sleep, we performed single-cell RNA sequencing.
2023-07-21 | GSE185369 | GEO
Project description:Aging is a complex process involving various systems and behavioral changes. Altered immune regulation, dysbiosis, oxidative stress, and sleep decline are common features of aging, but their interconnection is poorly understood. Using Drosophila, we discover that IM33, a novel immune modulator, and its mammalian homolog, secretory leukocyte protease inhibitor (SLPI), are upregulated in old flies and old mice, respectively. Knockdown of IM33 in glia elevates the gut reactive oxygen species (ROS) level and alters gut microbiota composition, including increased Lactiplantibacillus plantarum abundance, leading to a shortened lifespan. Additionally, dysbiosis induces sleep fragmentation through the activation of insulin-producing cells in the brain, which is mediated by the binding of Lactiplantibacillus plantarum-produced DAP-type peptidoglycan to the peptidoglycan recognition protein LE (PGRP-LE) receptor. Therefore, IM33 plays a role in the glia-microbiota-neuronal axis, connecting neuroinflammation, dysbiosis, and sleep decline during aging. Identifying molecular mediators of these processes could lead to the development of innovative strategies for extending lifespan.
| S-EPMC10592285 | biostudies-literature
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263928 | GEO
Project description:To investigate genome-wide gene expression changes induced by an NMDA receptor positive allosteric modulator in neuronal cultures using next-generation sequencing
2021-01-01 | GSE139080 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263929 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263927 | GEO
Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.
2024-05-24 | GSE263926 | GEO
Project description:Drosophila ensheathing glia decline in relative numbers during normal aging. Using p35, we inhibit apoptosis specifically in ensheathing glia, and show that this is sufficient to rescue the decline in ensheathing glia, improve neuromotor performance of aged flies, and increase lifespan. Remaining ensheathing glia from aged brains exhibit transcriptomes exhibiting signs of lipid metabolism and apoptosis dysregulation. Expanding ensheathing glia with p35 also prevented the accumulation of amyloid plaques and delayed premature death in a fly model of Alzheimer's disease.
2023-02-20 | GSE179604 | GEO
Project description:Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia cells (MG) that activate the proneural factor Achaete-scute homolog 1 (Ascl1/Mash1) and de-differentiate into progenitors cells. In contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether Ascl1 could restore a neurogenic potential to mammalian MG, we over-expressed Ascl1 in dissociated mouse MG cultures and intact retinal explants. Ascl1-infected MG upregulate retinal progenitor-specific genes, while downregulating glial genes. Furthermore, Ascl1 remodeled the chromatin at its targets from a repressive to active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers, and displayed neuron-like physiological responses. These results indicate that a single transcription factor, Ascl1, can produce a neurogenic state in mature Muller glia. Expresssion profiling was used to determine the genes that were changed after Ascl1 infection of P12 cultured Müller glia compared with those present in P0 progenitors and P7-P21 Müller glia Retinas were dissociated and FAC-sorted from Hes5-GFP mice at P0, P7, P10, P14 or P21 and submitted for profiling. WT Retinas were dissociated at P12, grown for 1 week in culture, and infected with lentiviruses expressing Ascl1 or GFP for four days. Total RNA was extracted and submitted for profiling.
2013-04-06 | E-GEOD-45835 | biostudies-arrayexpress