{"doi":"10.1101/2023.08.25.23294589","title":"Profiling an integrated network of cellular senescence and immune resilience measures in natural aging: a prospective multi-cohort study","abstract":"Background: Biological aging begins decades before the onset of age-related clinical conditions and is mediated by both cellular senescence and declining adaptive immune function. These processes are functionally related with the rate of senescent cell accumulation dependent upon a balance between induction and immune clearance. We previously showed that biomarkers in these domains can identify patients at-risk of surgery-related adverse events. Here, we describe evidence of clinical relevance in early aging and metabolic phenotypes in a general adult population. Methods: We enrolled a total of 482 participants (ages 25-90) into two prospective, cross-sectional healthy aging cohorts. Expression of biomarkers of adaptive immune function and cellular senescence (SapereX) was measured in CD3+ T cells isolated from peripheral blood. Findings: We established a network of biomarkers of adaptive immune function that correlate with cellular senescence and associate with early aging phenotypes. SapereX immune components associated with a decrease in CD4+ T cells, an increase in cytotoxic CD8+ T cells, and a loss of CD8+ naïve T cells (Pearson correlation 0.3-0.6). These components also associated with a metric of immune resilience, an ability to withstand antigen challenge and inflammation. In contrast, SapereX components were only weakly associated with GlycanAge (Pearson correlation 0.03-0.15) and commonly used DNA methylation clocks (Pearson correlation 0-0.25). Finally, SapereX biomarkers, in particular p16, were associated with chronic inflammation and metabolic dysregulation. Interpretation: Measurement of SapereX biomarkers may capture essential elements of the relationship between cellular senescence and dysregulated adaptive immune function and may provide a benchmark for clinically relevant health decisions.","journal":"medRxiv","year":2023,"id":400563,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9431,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1169400,"name":"Amy Entwistle","orcid":null,"position":1,"is_corresponding":false},{"id":913305,"name":"Anne K. Knecht","orcid":"0000-0003-4777-7880","position":2,"is_corresponding":false},{"id":913931,"name":"Susan L. Strum","orcid":null,"position":3,"is_corresponding":false},{"id":1177048,"name":"Allison Ross","orcid":"0000-0002-9645-7691","position":4,"is_corresponding":false},{"id":574627,"name":"Kirsten A. Nyrop","orcid":"0000-0002-2974-480X","position":5,"is_corresponding":false},{"id":535400,"name":"Hyman B. Muss","orcid":"0000-0003-2862-9970","position":6,"is_corresponding":false},{"id":325622,"name":"Denis Tsygankov","orcid":"0000-0002-1180-3584","position":7,"is_corresponding":false},{"id":1177375,"name":"Joseph M. Raffaele","orcid":null,"position":8,"is_corresponding":false},{"id":528939,"name":"Natalia Mitin","orcid":"0000-0003-4898-7716","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":"37693401","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":[]}