{"doi":"10.1101/2023.11.07.566050","title":"Single-cell transcriptomic and genomic changes in the aging human brain","abstract":"Aging brings dysregulation of various processes across organs and tissues, often stemming from stochastic damage to individual cells over time. Here, we used a combination of single-nucleus RNA-sequencing and single-cell whole-genome sequencing to identify transcriptomic and genomic changes in the prefrontal cortex of the human brain across life span, from infancy to centenarian. We identified infant-specific cell clusters enriched for the expression of neurodevelopmental genes, and a common down-regulation of cell-essential homeostatic genes that function in ribosomes, transport, and metabolism during aging across cell types. Conversely, expression of neuron-specific genes generally remains stable throughout life. We observed a decrease in specific DNA repair genes in aging, including genes implicated in generating brain somatic mutations as indicated by mutation signature analysis. Furthermore, we detected gene-length-specific somatic mutation rates that shape the transcriptomic landscape of the aged human brain. These findings elucidate critical aspects of human brain aging, shedding light on transcriptomic and genomics dynamics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390623,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8541,"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":43219,"name":"Tianxiong Yu","orcid":"0000-0003-1151-4624","position":1,"is_corresponding":false},{"id":842082,"name":"Jennifer S. Ziegenfuss","orcid":"0000-0002-3828-0381","position":2,"is_corresponding":false},{"id":810335,"name":"Allie K. Tolles","orcid":"0000-0002-5569-0710","position":3,"is_corresponding":false},{"id":1025899,"name":"Yerin Kim","orcid":"0000-0003-2121-8511","position":4,"is_corresponding":false},{"id":368,"name":"Zhiping Weng","orcid":"0000-0002-3032-7966","position":5,"is_corresponding":false},{"id":810338,"name":"Michael A. Lodato","orcid":"0000-0003-4175-1073","position":6,"is_corresponding":false},{"id":810334,"name":"Ailsa M. Jeffries","orcid":"0000-0001-6233-4215","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:18:37.743462Z","pmid":"37986960","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":[]}