Evidence map›Paper›PMID 27746093›Full record

ArticleCell systems2016

Defective Signaling in the JAK-STAT Pathway Tracks with Chronic Inflammation and Cardiovascular Risk in Aging Humans.

Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman and 6 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01827462 (Immune Senescence in the Elderly), which is not on this map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01827462 phase4completednot on this map

Immune Senescence in the Elderly: Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages

TypeinterventionalSponsorStanford UniversityRan2007 to 2017Enrolled136ConditionsInfluenzaArmsTrivalent, inactivated influenza vaccine (TIV), Quadrivalent, inactivated influenza vaccine (IIV4), High-Dose Trivalent, inactivated influenza vaccine (TIV High-Dose)
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. Epigenetic aging in Alzheimer's disease: Relation to proteome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Immune Aging is an Independent Risk Factor for Cardiovascular Disease.bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. The complicated relationship between inflammation and metabolic dysfunction.Journal of diabetes and metabolic disorders · 2025
    Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Immunological biomarkers of aging.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Review
  17. Review
  18. Review
  19. Article
  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Shai S Shen-OrrFaculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
David FurmanDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Brian A KiddDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Francois HadadDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Patricia LovelaceDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ying-Wen HuangDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yael Rosenberg-HassonDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sally MackeyDivision of Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fatemeh A Gomari GrisarDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yishai PickmanFaculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Holden T MaeckerDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yueh-Hsiu ChienDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cornelia L DekkerInstitute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joseph C WuDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Atul J ButteDivision of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: atul.butte@ucsf.edu.
Mark M DavisDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: mmdavis@stanford.edu.
Stanford University · USCardiovascular Institute of the South · USTechnion – Israel Institute of Technology · ILHoward Hughes Medical Institute · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1UL1RR025744 · NCRR · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2008 to 2011
$22.4M
Vaccination and infection: indicators of immunological health and responsivenessU19AI090019 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2010 to 2015
$17.3M
NCRR NIH HHS UL1 RR025744NIAID NIH HHS HHSN272201200028CNIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI090019
6 · The paper itself

Abstract

Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ. Baseline pSTAT levels tracked with circulating levels of C-reactive protein (CRP), and we derived a cytokine response score that negatively correlates with measures of cardiovascular disease, specifically diastolic dysfunction and atherosclerotic burden, outperforming CRP. Thus, we identified an immunological link between inflammation, decreased cell responsiveness in the JAK-STAT pathway, and cardiovascular aging. Targeting chronic inflammation may ameliorate this deficiency in cellular responsiveness and improve cardiovascular function.

Indexed as

Signal TransductionAgingCardiovascular DiseasesCytokinesHumansInflammationInterferon-gammaPhosphorylationRisk FactorsSTAT Transcription FactorsCytokinesInterferon-gammaSTAT Transcription Factorsagingcardiovascularcytokine responsesimmune monitoringimmune signalingimmunosenescenceinflammagingsystems immunology

Identifiers

PMID27746093
PMCPMC5358544
OpenAlexW2531162495

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.