{"doi":"10.1101/2022.07.06.498968","title":"Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity","abstract":"Abstract Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age. To identify immune-specific patterns of aging and extreme human longevity, we analyzed novel single cell profiles from the peripheral blood mononuclear cells (PBMCs) of 7 centenarians (mean age 106) and publicly available single cell RNA-sequencing (scRNA-seq) datasets that included an additional 7 centenarians as well as 52 people at younger ages (20-89 years). The analysis confirmed known shifts in the ratio of lymphocytes to myeloid cells, and noncytotoxic to cytotoxic cell distributions with aging, but also identified significant shifts from CD4 + T cell to B cell populations in centenarians suggesting a history of exposure to natural and environmental immunogens. Our transcriptional analysis identified cell type signatures specific to exceptional longevity that included genes with age-related changes (e.g., increased expression of STK17A , a gene known to be involved in DNA damage response ) as well as genes expressed uniquely in centenarians’ PBMCs (e.g., S100A4 , part of the S100 protein family studied in age-related disease and connected to longevity and metabolic regulation ) . Collectively, these data suggest that centenarians harbor unique, highly functional immune systems that have successfully adapted to a history of insults allowing for the achievement of exceptional longevity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298305,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9444,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":420359,"name":"Todd W. Dowrey","orcid":"0000-0001-6086-6306","position":1,"is_corresponding":false},{"id":89670,"name":"Carlos Villacorta-Martín","orcid":"0000-0002-1350-465X","position":2,"is_corresponding":false},{"id":850666,"name":"Monty Montano","orcid":"0000-0001-8738-2838","position":3,"is_corresponding":false},{"id":375680,"name":"Eric Reed","orcid":"0000-0003-2347-720X","position":4,"is_corresponding":false},{"id":407424,"name":"Stacy L. Andersen","orcid":"0000-0002-2442-6386","position":5,"is_corresponding":false},{"id":475749,"name":"Thomas T. Perls","orcid":"0000-0002-2492-4334","position":6,"is_corresponding":false},{"id":25431,"name":"Stefano Monti","orcid":"0000-0002-9376-0660","position":7,"is_corresponding":false},{"id":340206,"name":"George J. Murphy","orcid":"0000-0003-3464-793X","position":8,"is_corresponding":false},{"id":326888,"name":"Paola Sebastiani","orcid":"0000-0001-6419-1545","position":9,"is_corresponding":false},{"id":344561,"name":"Tanya T. Karagiannis","orcid":"0000-0003-4065-495X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:36.269611Z","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":[]}