{"doi":"10.4049/jimmunol.184.supp.138.2","title":"A Systemic age dependent defect in immune-cell signaling response induced by inflammation (138.2)","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Immune system function generally degrades with age and is associated with increased risk of infection and disease. Though differences between young and old have been noted in many immune system components, no system wide understanding of how these disparate observation act together exists to date, nor how they relate to genes found to associated with increased longevity, many of which are immune related. Here we characterize the immune system of 29 young and old individuals by concurrently measuring from peripheral blood, immune cell subset frequency, serum cytokines, gene expression and individual cellular responses to cytokine stimuli by pathway specific phospho-protein abundance. We identify age-dependent changes in STAT signaling baseline and in response to stimulation by a panel of 7 different cytokines, particularly prominent in CD8 and CD4 T cells, but also in monocytes and B-cells. The observed differences in cellular responses are not due to adaptation to higher level of cytokine stimuli but rather to an inert inability to mount a full response, many times augmented by a higher base line phosphorylation level in the elderly. We construct an immune network spanning multiple biological layers and identify co-occurring modules which link longevity associated genes with these cellular immune phenotypes. We quantify the contributions of these modules to the observed reduction in cellular response to stimuli in the elderly and suggest a common responsible mechanism.</jats:p>","journal":"The Journal of Immunology","year":2010,"id":3382,"datarank":0.1374946315919635,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.033522554507971696,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.033522554507971696,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0587,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2010-04-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3338,"name":"David Furman","orcid":"0000-0002-3654-9519","position":1,"is_corresponding":false},{"id":12999,"name":"Brian Kidd","orcid":"0000-0003-2110-1145","position":2,"is_corresponding":false},{"id":7903,"name":"Mark Davis","orcid":null,"position":6,"is_corresponding":false},{"id":3339,"name":"Shai S. Shen-Orr","orcid":"0000-0002-6991-7736","position":7,"is_corresponding":false},{"id":3342,"name":"Holden T. Maecker","orcid":"0000-0003-0795-9946","position":8,"is_corresponding":false},{"id":3340,"name":"Cornelia L. Dekker","orcid":"0000-0002-3871-918X","position":9,"is_corresponding":false},{"id":51,"name":"Atul Janardhan Butte","orcid":"0000-0002-7433-2740","position":10,"is_corresponding":false},{"id":3343,"name":"Mark M. Davis","orcid":"0000-0001-6868-657X","position":11,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}