Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context
Summary: Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inte...
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Elsevier
2025-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000027 |
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| author | Lennart Riemann Rodrigo Gutierrez Ivan Odak Joana Barros-Martins Lennart M. Roesner Ximena Leon Lara Christine Falk Thomas F. Schulz Gesine Hansen Thomas Werfel Reinhold Förster Berislav Bošnjak Felix Jenniches Norman Klopp Till Robin Lesker Martin Stangel |
| author_facet | Lennart Riemann Rodrigo Gutierrez Ivan Odak Joana Barros-Martins Lennart M. Roesner Ximena Leon Lara Christine Falk Thomas F. Schulz Gesine Hansen Thomas Werfel Reinhold Förster Berislav Bošnjak Felix Jenniches Norman Klopp Till Robin Lesker Martin Stangel |
| author_sort | Lennart Riemann |
| collection | DOAJ |
| description | Summary: Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability. Methods: We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20–40 years) from the RESIST Senior Individuals (SI) cohort. Extensive demographic, clinical, and laboratory data were collected. Multi-color spectral flow cytometry and 48-plex plasma cytokine assays were used for deep immune phenotyping. Data were analyzed using unsupervised clustering and multi-dataset integration approaches. Findings: We studied 97 innate and adaptive immune cell populations, revealing intricate age- and sex-related changes in the elderly immune system. Our large sample size allowed detection of even subtle changes in cytokines and immune cell clusters. Integrative analysis combining clinical, laboratory, and immunological data revealed systems-level aging signatures, including shifts in specific immune cell subpopulations and cytokine concentrations (e.g., HGF and CCL27). Additionally, we identified unique immune signatures associated with smoking, obesity, and diseases such as osteoporosis, heart failure, and gout. Interpretation: This study provides one of the most comprehensive immune profiles of elderly individuals, uncovering high-resolution immune changes associated with aging. Our findings highlight clinically relevant immune signatures that enhance our understanding of aging-related diseases and could guide future research into new treatments, offering translational insights into human health and aging. Funding: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2155—project number 390874280. |
| format | Article |
| id | doaj-art-9b655d52ef5d48fb9d35701cf36e45de |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-9b655d52ef5d48fb9d35701cf36e45de2025-01-26T05:04:05ZengElsevierEBioMedicine2352-39642025-02-01112105558Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in contextLennart Riemann0Rodrigo Gutierrez1Ivan Odak2Joana Barros-Martins3Lennart M. Roesner4Ximena Leon Lara5Christine Falk6Thomas F. Schulz7Gesine Hansen8Thomas Werfel9Reinhold Förster10Berislav BošnjakFelix JennichesNorman KloppTill Robin LeskerMartin StangelInstitute of Immunology, Hannover Medical School, Hannover, Germany; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Corresponding author. Institute of Immunology, Hannover Medical School, Hannover, Germany.Institute of Immunology, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, Germany; The Tisch Cancer Institute, Icahn School of Medicine, New York, USAInstitute of Immunology, Hannover Medical School, Hannover, Germany; Department of Microbiology and Immunology, Columbia University Medical Center, New York, USADepartment of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyInstitute of Transplantation Immunology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research, Partner Site Hannover-Braunschweig, Hannover, GermanyCluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; German Centre for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany; Institute of Virology, Hannover Medical School, Hannover, GermanyDepartment of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; German Center of Lung Research (DZL), BREATH, Hannover, GermanyDepartment of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; German Centre for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany; Corresponding author. Institute of Immunology, Hannover Medical School, Hannover, Germany.Summary: Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability. Methods: We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20–40 years) from the RESIST Senior Individuals (SI) cohort. Extensive demographic, clinical, and laboratory data were collected. Multi-color spectral flow cytometry and 48-plex plasma cytokine assays were used for deep immune phenotyping. Data were analyzed using unsupervised clustering and multi-dataset integration approaches. Findings: We studied 97 innate and adaptive immune cell populations, revealing intricate age- and sex-related changes in the elderly immune system. Our large sample size allowed detection of even subtle changes in cytokines and immune cell clusters. Integrative analysis combining clinical, laboratory, and immunological data revealed systems-level aging signatures, including shifts in specific immune cell subpopulations and cytokine concentrations (e.g., HGF and CCL27). Additionally, we identified unique immune signatures associated with smoking, obesity, and diseases such as osteoporosis, heart failure, and gout. Interpretation: This study provides one of the most comprehensive immune profiles of elderly individuals, uncovering high-resolution immune changes associated with aging. Our findings highlight clinically relevant immune signatures that enhance our understanding of aging-related diseases and could guide future research into new treatments, offering translational insights into human health and aging. Funding: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2155—project number 390874280.http://www.sciencedirect.com/science/article/pii/S2352396425000027Systems biologyAgingDeep immune phenotypingCytokinesSpectral flow cytometry |
| spellingShingle | Lennart Riemann Rodrigo Gutierrez Ivan Odak Joana Barros-Martins Lennart M. Roesner Ximena Leon Lara Christine Falk Thomas F. Schulz Gesine Hansen Thomas Werfel Reinhold Förster Berislav Bošnjak Felix Jenniches Norman Klopp Till Robin Lesker Martin Stangel Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context EBioMedicine Systems biology Aging Deep immune phenotyping Cytokines Spectral flow cytometry |
| title | Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context |
| title_full | Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context |
| title_fullStr | Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context |
| title_full_unstemmed | Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context |
| title_short | Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context |
| title_sort | integrative deep immune profiling of the elderly reveals systems level signatures of aging sex smoking and clinical traitsresearch in context |
| topic | Systems biology Aging Deep immune phenotyping Cytokines Spectral flow cytometry |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000027 |
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