Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice
We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects ar...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12550 |
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| author | Nicholas F. Fitz Amrita Sahu Yi Lu Fabrisia Ambrosio Iliya Lefterov Radosveta Koldamova |
| author_facet | Nicholas F. Fitz Amrita Sahu Yi Lu Fabrisia Ambrosio Iliya Lefterov Radosveta Koldamova |
| author_sort | Nicholas F. Fitz |
| collection | DOAJ |
| description | We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport. Comparing the differentially expressed genes to recently published chronological aging clock genes reveals a reversal of transcriptomic aging in the choroid plexus. Following young serum treatment, the hippocampal transcriptome demonstrates significant upregulation of the anti-aging gene Klotho, along with an abrogated effect after EV depletion. Transcriptomic profiling of Klotho knockout and heterozygous mice shows the downregulation of genes associated with transport, exocytosis, and lipid transport, while upregulated genes are associated with activated microglia. The results of our study indicate the significance of EVs as vehicles to deliver signals from the periphery to the brain and the importance of Klotho in maintaining brain homeostasis. |
| first_indexed | 2024-03-10T23:53:18Z |
| format | Article |
| id | doaj.art-5bd0a29701494c8fa9ad0f289c6ed6ad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:53:18Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5bd0a29701494c8fa9ad0f289c6ed6ad2023-11-19T01:24:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161255010.3390/ijms241612550Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old MiceNicholas F. Fitz0Amrita Sahu1Yi Lu2Fabrisia Ambrosio3Iliya Lefterov4Radosveta Koldamova5Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02115, USADepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USAWe have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport. Comparing the differentially expressed genes to recently published chronological aging clock genes reveals a reversal of transcriptomic aging in the choroid plexus. Following young serum treatment, the hippocampal transcriptome demonstrates significant upregulation of the anti-aging gene Klotho, along with an abrogated effect after EV depletion. Transcriptomic profiling of Klotho knockout and heterozygous mice shows the downregulation of genes associated with transport, exocytosis, and lipid transport, while upregulated genes are associated with activated microglia. The results of our study indicate the significance of EVs as vehicles to deliver signals from the periphery to the brain and the importance of Klotho in maintaining brain homeostasis.https://www.mdpi.com/1422-0067/24/16/12550extracellular vesiclesagingchoroid plexushippocampusmemoryklotho |
| spellingShingle | Nicholas F. Fitz Amrita Sahu Yi Lu Fabrisia Ambrosio Iliya Lefterov Radosveta Koldamova Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice International Journal of Molecular Sciences extracellular vesicles aging choroid plexus hippocampus memory klotho |
| title | Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice |
| title_full | Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice |
| title_fullStr | Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice |
| title_full_unstemmed | Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice |
| title_short | Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice |
| title_sort | extracellular vesicles in young serum contribute to the restoration of age related brain transcriptomes and cognition in old mice |
| topic | extracellular vesicles aging choroid plexus hippocampus memory klotho |
| url | https://www.mdpi.com/1422-0067/24/16/12550 |
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