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Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring
Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single‐cell transcriptomic analysis of per...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799020/ https://www.ncbi.nlm.nih.gov/pubmed/36354175 http://dx.doi.org/10.1002/advs.202204849 |
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author | Dong, Chen Miao, Ya‐ru Zhao, Rui Yang, Mei Guo, An‐yuan Xue, Zhong‐hui Li, Teng Zhang, Qiong Bao, Yanfeng Shen, Chen Sun, Chi Yang, Ying Gu, Xi‐xi Jin, Yi Li, Rong Xu, Min Guo, Jia‐xin Zong, Zhi‐ying Zhou, Wei He, Mei Wang, Dan‐ni Su, Jian‐you Zhang, Xiao‐ming Zeng, Xu‐hui Gao, Jian‐lin Gu, Zhi‐feng |
author_facet | Dong, Chen Miao, Ya‐ru Zhao, Rui Yang, Mei Guo, An‐yuan Xue, Zhong‐hui Li, Teng Zhang, Qiong Bao, Yanfeng Shen, Chen Sun, Chi Yang, Ying Gu, Xi‐xi Jin, Yi Li, Rong Xu, Min Guo, Jia‐xin Zong, Zhi‐ying Zhou, Wei He, Mei Wang, Dan‐ni Su, Jian‐you Zhang, Xiao‐ming Zeng, Xu‐hui Gao, Jian‐lin Gu, Zhi‐feng |
author_sort | Dong, Chen |
collection | PubMed |
description | Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single‐cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians’ offspring (CO), and nine offspring spouses or neighbors (Control, age‐matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic‐phenotype‐clusters (CPC) and the naïve‐phenotype‐clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8(+) T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T‐cell‐receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK(+) CD8 cells during aging, centenarians show accumulation of GZMB(+) and CMC1(+) CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging. |
format | Online Article Text |
id | pubmed-9799020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97990202023-01-05 Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring Dong, Chen Miao, Ya‐ru Zhao, Rui Yang, Mei Guo, An‐yuan Xue, Zhong‐hui Li, Teng Zhang, Qiong Bao, Yanfeng Shen, Chen Sun, Chi Yang, Ying Gu, Xi‐xi Jin, Yi Li, Rong Xu, Min Guo, Jia‐xin Zong, Zhi‐ying Zhou, Wei He, Mei Wang, Dan‐ni Su, Jian‐you Zhang, Xiao‐ming Zeng, Xu‐hui Gao, Jian‐lin Gu, Zhi‐feng Adv Sci (Weinh) Research Articles Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single‐cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians’ offspring (CO), and nine offspring spouses or neighbors (Control, age‐matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic‐phenotype‐clusters (CPC) and the naïve‐phenotype‐clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8(+) T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T‐cell‐receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK(+) CD8 cells during aging, centenarians show accumulation of GZMB(+) and CMC1(+) CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging. John Wiley and Sons Inc. 2022-11-10 /pmc/articles/PMC9799020/ /pubmed/36354175 http://dx.doi.org/10.1002/advs.202204849 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Dong, Chen Miao, Ya‐ru Zhao, Rui Yang, Mei Guo, An‐yuan Xue, Zhong‐hui Li, Teng Zhang, Qiong Bao, Yanfeng Shen, Chen Sun, Chi Yang, Ying Gu, Xi‐xi Jin, Yi Li, Rong Xu, Min Guo, Jia‐xin Zong, Zhi‐ying Zhou, Wei He, Mei Wang, Dan‐ni Su, Jian‐you Zhang, Xiao‐ming Zeng, Xu‐hui Gao, Jian‐lin Gu, Zhi‐feng Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title | Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title_full | Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title_fullStr | Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title_full_unstemmed | Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title_short | Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring |
title_sort | single‐cell transcriptomics reveals longevity immune remodeling features shared by centenarians and their offspring |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799020/ https://www.ncbi.nlm.nih.gov/pubmed/36354175 http://dx.doi.org/10.1002/advs.202204849 |
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