{"doi":"10.1007/s11357-022-00645-w","title":"Old plasma dilution reduces human biological age: a clinical study","abstract":"This work extrapolates to humans the previous animal studies on blood heterochronicity and establishes a novel direct measurement of biological age. Our results support the hypothesis that, similar to mice, human aging is driven by age-imposed systemic molecular excess, the attenuation of which reverses biological age, defined in our work as a deregulation (noise) of 10 novel protein biomarkers. The results on biological age are strongly supported by the data, which demonstrates that rounds of therapeutic plasma exchange (TPE) promote a global shift to a younger systemic proteome, including youthfully restored pro-regenerative, anticancer, and apoptotic regulators and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Mechanistically, the circulatory regulators of the JAK-STAT, MAPK, TGF-beta, NF-κB, and Toll-like receptor signaling pathways become more youthfully balanced through normalization of TLR4, which we define as a nodal point of this molecular rejuvenation. The significance of our findings is confirmed through big-data gene expression studies.","journal":"GeroScience","year":2022,"id":241304,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":276310,"name":"D Kiprov","orcid":null,"position":1,"is_corresponding":false},{"id":870041,"name":"Connor Luellen","orcid":"0000-0001-8841-9727","position":2,"is_corresponding":false},{"id":276309,"name":"Michael Lieb","orcid":null,"position":3,"is_corresponding":false},{"id":274225,"name":"Chao Liu","orcid":"0000-0001-8683-3473","position":4,"is_corresponding":false},{"id":870042,"name":"Etsuko Watanabe","orcid":"0000-0003-3533-1670","position":5,"is_corresponding":false},{"id":870647,"name":"Xiaoyue Mei","orcid":null,"position":6,"is_corresponding":false},{"id":870648,"name":"Kaitlin Cassaleto","orcid":null,"position":7,"is_corresponding":false},{"id":253924,"name":"Joel H. Kramer","orcid":"0000-0002-2917-8297","position":8,"is_corresponding":false},{"id":274228,"name":"Michael J. Conboy","orcid":"0000-0002-6434-4772","position":9,"is_corresponding":false},{"id":274229,"name":"Irina M. Conboy","orcid":"0000-0002-4276-0644","position":10,"is_corresponding":false},{"id":572476,"name":"Dae‐Hwan Kim","orcid":"0000-0001-8746-6177","position":0,"is_corresponding":true}],"reference_count":124,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"35999337","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":[]}