Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring
Abstract 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 analys...
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202204849 |
| _version_ | 1797974982079283200 |
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| author | Chen Dong Ya‐ru Miao Rui Zhao Mei Yang An‐yuan Guo Zhong‐hui Xue Teng Li Qiong Zhang Yanfeng Bao Chen Shen Chi Sun Ying Yang Xi‐xi Gu Yi Jin Rong Li Min Xu Jia‐xin Guo Zhi‐ying Zong Wei Zhou Mei He Dan‐ni Wang Jian‐you Su Xiao‐ming Zhang Xu‐hui Zeng Jian‐lin Gao Zhi‐feng Gu |
| author_facet | Chen Dong Ya‐ru Miao Rui Zhao Mei Yang An‐yuan Guo Zhong‐hui Xue Teng Li Qiong Zhang Yanfeng Bao Chen Shen Chi Sun Ying Yang Xi‐xi Gu Yi Jin Rong Li Min Xu Jia‐xin Guo Zhi‐ying Zong Wei Zhou Mei He Dan‐ni Wang Jian‐you Su Xiao‐ming Zhang Xu‐hui Zeng Jian‐lin Gao Zhi‐feng Gu |
| author_sort | Chen Dong |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T04:28:23Z |
| format | Article |
| id | doaj.art-92a306777f614196a2cc3df9cb5d91a4 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T04:28:23Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-92a306777f614196a2cc3df9cb5d91a42022-12-29T14:19:16ZengWileyAdvanced Science2198-38442022-12-01936n/an/a10.1002/advs.202204849Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their OffspringChen Dong0Ya‐ru Miao1Rui Zhao2Mei Yang3An‐yuan Guo4Zhong‐hui Xue5Teng Li6Qiong Zhang7Yanfeng Bao8Chen Shen9Chi Sun10Ying Yang11Xi‐xi Gu12Yi Jin13Rong Li14Min Xu15Jia‐xin Guo16Zhi‐ying Zong17Wei Zhou18Mei He19Dan‐ni Wang20Jian‐you Su21Xiao‐ming Zhang22Xu‐hui Zeng23Jian‐lin Gao24Zhi‐feng Gu25Research Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaCenter for Artificial Intelligence Biology Hubei Bioinformatics & Molecular Imaging Key Laboratory Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430074 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaCenter for Artificial Intelligence Biology Hubei Bioinformatics & Molecular Imaging Key Laboratory Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430074 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaKey Laboratory of Molecular Virology & Immunology Institut Pasteur of Shanghai Chinese Academy of Sciences Shanghai 200025 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaDepartment of Geriatrics Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaLaboratory Center Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaInstitute of Reproductive Medicine Medical School Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaResearch Center of Clinical Medicine Research Center of Gerontology and Longevity Key Laboratory of Immunology Research Center of Nursing Department of Rheumatology Affiliated Hospital of Nantong University Nantong University Nantong 226001 ChinaAbstract 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.https://doi.org/10.1002/advs.202204849centenarianimmune remodelinglongevitysingle‐cell transcriptomeT cell |
| spellingShingle | Chen Dong Ya‐ru Miao Rui Zhao Mei Yang An‐yuan Guo Zhong‐hui Xue Teng Li Qiong Zhang Yanfeng Bao Chen Shen Chi Sun Ying Yang Xi‐xi Gu Yi Jin Rong Li Min Xu Jia‐xin Guo Zhi‐ying Zong Wei Zhou Mei He Dan‐ni Wang Jian‐you Su Xiao‐ming Zhang Xu‐hui Zeng Jian‐lin Gao Zhi‐feng Gu Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring Advanced Science centenarian immune remodeling longevity single‐cell transcriptome T cell |
| 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 | centenarian immune remodeling longevity single‐cell transcriptome T cell |
| url | https://doi.org/10.1002/advs.202204849 |
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