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A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. W...

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Autores principales: Saul, Dominik, Kosinsky, Robyn Laura, Atkinson, Elizabeth J., Doolittle, Madison L., Zhang, Xu, LeBrasseur, Nathan K., Pignolo, Robert J., Robbins, Paul D., Niedernhofer, Laura J., Ikeno, Yuji, Jurk, Diana, Passos, João F., Hickson, LaTonya J., Xue, Ailing, Monroe, David G., Tchkonia, Tamara, Kirkland, James L., Farr, Joshua N., Khosla, Sundeep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381717/
https://www.ncbi.nlm.nih.gov/pubmed/35974106
http://dx.doi.org/10.1038/s41467-022-32552-1
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author Saul, Dominik
Kosinsky, Robyn Laura
Atkinson, Elizabeth J.
Doolittle, Madison L.
Zhang, Xu
LeBrasseur, Nathan K.
Pignolo, Robert J.
Robbins, Paul D.
Niedernhofer, Laura J.
Ikeno, Yuji
Jurk, Diana
Passos, João F.
Hickson, LaTonya J.
Xue, Ailing
Monroe, David G.
Tchkonia, Tamara
Kirkland, James L.
Farr, Joshua N.
Khosla, Sundeep
author_facet Saul, Dominik
Kosinsky, Robyn Laura
Atkinson, Elizabeth J.
Doolittle, Madison L.
Zhang, Xu
LeBrasseur, Nathan K.
Pignolo, Robert J.
Robbins, Paul D.
Niedernhofer, Laura J.
Ikeno, Yuji
Jurk, Diana
Passos, João F.
Hickson, LaTonya J.
Xue, Ailing
Monroe, David G.
Tchkonia, Tamara
Kirkland, James L.
Farr, Joshua N.
Khosla, Sundeep
author_sort Saul, Dominik
collection PubMed
description Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs.
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spelling pubmed-93817172022-08-18 A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues Saul, Dominik Kosinsky, Robyn Laura Atkinson, Elizabeth J. Doolittle, Madison L. Zhang, Xu LeBrasseur, Nathan K. Pignolo, Robert J. Robbins, Paul D. Niedernhofer, Laura J. Ikeno, Yuji Jurk, Diana Passos, João F. Hickson, LaTonya J. Xue, Ailing Monroe, David G. Tchkonia, Tamara Kirkland, James L. Farr, Joshua N. Khosla, Sundeep Nat Commun Article Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs. Nature Publishing Group UK 2022-08-16 /pmc/articles/PMC9381717/ /pubmed/35974106 http://dx.doi.org/10.1038/s41467-022-32552-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Saul, Dominik
Kosinsky, Robyn Laura
Atkinson, Elizabeth J.
Doolittle, Madison L.
Zhang, Xu
LeBrasseur, Nathan K.
Pignolo, Robert J.
Robbins, Paul D.
Niedernhofer, Laura J.
Ikeno, Yuji
Jurk, Diana
Passos, João F.
Hickson, LaTonya J.
Xue, Ailing
Monroe, David G.
Tchkonia, Tamara
Kirkland, James L.
Farr, Joshua N.
Khosla, Sundeep
A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title_full A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title_fullStr A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title_full_unstemmed A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title_short A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
title_sort new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381717/
https://www.ncbi.nlm.nih.gov/pubmed/35974106
http://dx.doi.org/10.1038/s41467-022-32552-1
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