Age-dependent cytokine surge in blood precedes cancer diagnosis
Abstract
Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome Atlas. We found that a similar set of cytokines is upregulated in tumor tissues, specifically after the age of 80 y. Similarly, cellular senescence activity and CDKN1A/p21 expression increase with age in cancer tissues. Finally, we demonstrated that the cytokine levels in serum can be used to predict cancers among subjects age at 80+ y. Our results suggest that latent senescent cancers contribute to age-related chronic inflammation.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Guangbo Chen
Department of Microbiology and Immunology, Stanford University School of Medicine
Azam Mohsin
Department of Microbiology and Immunology, Stanford University School of Medicine
Hong Zheng
Center of Nanomaterials for Renewable Energy, State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering
Yael Rosenberg-Hasson
Department of Microbiology and Immunology, Stanford University School of Medicine
Cindy Padilla
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine
Kavita Y. Sarin
Department of Dermatology, School of Medicine, Stanford University
Cornelia L. Dekker
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine
Philip Grant
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine
Holden T. Maecker
Department of Microbiology and Immunology, Stanford University School of Medicine
Ying Lu
David Furman
Buck Institute for Research on Aging
Shai Shen-Orr
Department of Immunology, Faculty of Medicine, Technion Israel Institute of Technology
Purvesh Khatri
Department of Microbiology and Immunology, Stanford University School of Medicine
Mark M. Davis
Institute of Immunity, Transplantation and Infection, Stanford University