{"doi":"10.3389/fgene.2021.796547","title":"Increased Rate of Epigenetic Aging in Men Living With HIV Prior to Treatment","abstract":"Background: Epigenetic aging is accelerated in tissues of persons living with HIV (PLWH) and may underlie the early onset of age-related illnesses. This study examines the rate-of-change in epigenetic age in PLWH following HIV infection but before HAART, using archived longitudinal samples from the Multicenter AIDS Cohort Study. Methods: DNA was isolated from cryopreserved peripheral blood mononuclear cells from 101 men living with HIV, with baseline visit <2.5 years after HIV seroconversion (Visit 1) and follow-up visit <1.5 years before the initiation of HAART (Visit 2), and 100 HIV-uninfected men matched on age and visits with comparable time intervals. DNA methylation (DNAm) age was estimated for five clocks (Pan-tissue, Extrinsic, Phenotypic, Grim, and Skin & Blood age), and a DNAm-based estimate of telomere length (DNAmTL). Multivariate linear regression models were used to examine baseline factors associated with rate-of-aging, defined as (DNAm age visit 2–DNAm age visit 1)/(age visit 2–age visit 1). Results: Epigenetic age increased approximately twice as fast in PLWH as uninfected controls (Pan-tissue, Extrinsic, and Phenotypic clocks). Shortening of DNAmTL was nearly 3-fold faster in PLWH than controls. Faster rate-of-aging was associated with HIV status (Pan-Tissue, Extrinsic, Phenotypic, and DNAmTL), white race (Extrinsic, DNAmTL), higher cumulative HIV viral load (Grim), and lower baseline DNAm age (Phenotypic, Skin & Blood). Conclusion: Epigenetic rates-of-aging were significantly faster for untreated PLWH. Our findings expand on the important impact of HIV infection on biologic aging, both in elevating epigenetic age and increasing the rate-of-aging in the years following infection.","journal":"Frontiers in Genetics","year":2022,"id":251667,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9335,"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":337739,"name":"Elizabeth C. Breen","orcid":"0000-0001-6046-4999","position":1,"is_corresponding":false},{"id":482212,"name":"Roger Shih","orcid":null,"position":2,"is_corresponding":false},{"id":895601,"name":"Larry Chen","orcid":null,"position":3,"is_corresponding":false},{"id":895097,"name":"Ruibin Wang","orcid":"0000-0002-5887-9009","position":4,"is_corresponding":false},{"id":38267,"name":"Steve Horvath","orcid":"0000-0002-4110-3589","position":5,"is_corresponding":false},{"id":292653,"name":"Jay H. Bream","orcid":"0000-0002-9149-7643","position":6,"is_corresponding":false},{"id":115227,"name":"Priya Duggal","orcid":"0000-0001-5809-2081","position":7,"is_corresponding":false},{"id":292654,"name":"Jeremy Martinson","orcid":"0000-0003-4673-7238","position":8,"is_corresponding":false},{"id":56243,"name":"Steven M. Wolinsky","orcid":"0000-0002-9625-6697","position":9,"is_corresponding":false},{"id":481568,"name":"Otoniel Martı́nez-Maza","orcid":"0000-0003-1364-0675","position":10,"is_corresponding":false},{"id":376707,"name":"Christina M. Ramirez","orcid":"0000-0002-8435-0416","position":11,"is_corresponding":false},{"id":95191,"name":"Beth D. Jamieson","orcid":"0000-0003-1206-3853","position":12,"is_corresponding":false},{"id":298118,"name":"Mary E. Sehl","orcid":"0000-0003-2301-0562","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:41.993282Z","pmid":"35295196","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":[]}