Journal
CELL SYSTEMS
Volume 3, Issue 4, Pages 374-+Publisher
CELL PRESS
DOI: 10.1016/j.cels.2016.09.009
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Funding
- Ellison Medical Foundation
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases [U19 AI057229, U19 AI090019, HHSN272201200028C, BWF IRSA 1015009, AHA 13EIA14420025]
- Clinical and Translational Science Award for the Stanford Center for Clinical and Translational Education and Research (Spectrum) from the National Center for Research Resources, National Institutes of Health [5UL1 RR025744]
- Israeli Science Foundation [1365/12]
- Stanford Cardiovascular Institute
- Stanford Center on Longevity
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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 alpha (IFN-alpha), and, to a lesser extent, IL-21 and IFN-gamma. 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.
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