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Transcriptomic reprogramming for neuronal age reversal
Aging is a progressive multifaceted functional decline of a biological system. Chronic age-related conditions such as neurodegenerative diseases are leading causes of death worldwide, and they are becoming a pressing problem for our society. To address this global challenge, there is a need for nove...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066999/ https://www.ncbi.nlm.nih.gov/pubmed/37004545 http://dx.doi.org/10.1007/s00439-023-02529-1 |
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author | Plesa, Alexandru M. Shadpour, Michael Boyden, Ed Church, George M. |
author_facet | Plesa, Alexandru M. Shadpour, Michael Boyden, Ed Church, George M. |
author_sort | Plesa, Alexandru M. |
collection | PubMed |
description | Aging is a progressive multifaceted functional decline of a biological system. Chronic age-related conditions such as neurodegenerative diseases are leading causes of death worldwide, and they are becoming a pressing problem for our society. To address this global challenge, there is a need for novel, safe, and effective rejuvenation therapies aimed at reversing age-related phenotypes and improving human health. With gene expression being a key determinant of cell identity and function, and in light of recent studies reporting rejuvenation effects through genetic perturbations, we propose an age reversal strategy focused on reprogramming the cell transcriptome to a youthful state. To this end, we suggest using transcriptomic data from primary human cells to predict rejuvenation targets and develop high-throughput aging assays, which can be used in large perturbation screens. We propose neural cells as particularly relevant targets for rejuvenation due to substantial impact of neurodegeneration on human frailty. Of all cell types in the brain, we argue that glutamatergic neurons, neuronal stem cells, and oligodendrocytes represent the most impactful and tractable targets. Lastly, we provide experimental designs for anti-aging reprogramming screens that will likely enable the development of neuronal age reversal therapies, which hold promise for dramatically improving human health. |
format | Online Article Text |
id | pubmed-10066999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-100669992023-04-03 Transcriptomic reprogramming for neuronal age reversal Plesa, Alexandru M. Shadpour, Michael Boyden, Ed Church, George M. Hum Genet Perspective Aging is a progressive multifaceted functional decline of a biological system. Chronic age-related conditions such as neurodegenerative diseases are leading causes of death worldwide, and they are becoming a pressing problem for our society. To address this global challenge, there is a need for novel, safe, and effective rejuvenation therapies aimed at reversing age-related phenotypes and improving human health. With gene expression being a key determinant of cell identity and function, and in light of recent studies reporting rejuvenation effects through genetic perturbations, we propose an age reversal strategy focused on reprogramming the cell transcriptome to a youthful state. To this end, we suggest using transcriptomic data from primary human cells to predict rejuvenation targets and develop high-throughput aging assays, which can be used in large perturbation screens. We propose neural cells as particularly relevant targets for rejuvenation due to substantial impact of neurodegeneration on human frailty. Of all cell types in the brain, we argue that glutamatergic neurons, neuronal stem cells, and oligodendrocytes represent the most impactful and tractable targets. Lastly, we provide experimental designs for anti-aging reprogramming screens that will likely enable the development of neuronal age reversal therapies, which hold promise for dramatically improving human health. Springer Berlin Heidelberg 2023-04-01 2023 /pmc/articles/PMC10066999/ /pubmed/37004545 http://dx.doi.org/10.1007/s00439-023-02529-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Perspective Plesa, Alexandru M. Shadpour, Michael Boyden, Ed Church, George M. Transcriptomic reprogramming for neuronal age reversal |
title | Transcriptomic reprogramming for neuronal age reversal |
title_full | Transcriptomic reprogramming for neuronal age reversal |
title_fullStr | Transcriptomic reprogramming for neuronal age reversal |
title_full_unstemmed | Transcriptomic reprogramming for neuronal age reversal |
title_short | Transcriptomic reprogramming for neuronal age reversal |
title_sort | transcriptomic reprogramming for neuronal age reversal |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066999/ https://www.ncbi.nlm.nih.gov/pubmed/37004545 http://dx.doi.org/10.1007/s00439-023-02529-1 |
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