Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traitsResearch in context
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
Affiliations
Lennart Riemann
Institute 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.
Rodrigo Gutierrez
Institute of Immunology, Hannover Medical School, Hannover, Germany
Ivan Odak
Institute of Immunology, Hannover Medical School, Hannover, Germany; The Tisch Cancer Institute, Icahn School of Medicine, New York, USA
Joana Barros-Martins
Institute of Immunology, Hannover Medical School, Hannover, Germany; Department of Microbiology and Immunology, Columbia University Medical Center, New York, USA
Lennart M. Roesner
Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
Ximena Leon Lara
Institute of Immunology, Hannover Medical School, Hannover, Germany
Christine Falk
Institute of Transplantation Immunology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany
Thomas F. Schulz
Cluster 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, Germany
Gesine Hansen
Department 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, Germany
Thomas Werfel
Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
Reinhold Förster
Institute 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.
