Age-dependent cytokine surge in blood precedes cancer diagnosis

• 成果类型: Article
• 署名作者: Chen, Guangbo; Mohsin, Azam; Zheng, Hong; Rosenberg -Hasson, Yael; Padilla, Cindy; Sarin, Kavita Y.; Dekker, Cornelia L.; Grant, Philip; Maecker, Holden T.; Lu, Ying; Furman, David; Orr, Shai; Khatri, Purvesh; Davis, Mark M.
• 署名单位: Medical College of Wisconsin; Medical College of Wisconsin; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Buck Institute for Research on Aging; Stanford University; University of Southern California; Technion Israel Institute of Technology; Rappaport Faculty of Medicine
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11279
• DOI: 10.1073/pnas.2420502122
• 发表日期: 2025-03-25
• 关键词: cellular senescence; skin-cancer; inflammation; repair; mechanisms; patterns; cells; older

摘要

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.