{"doi":"10.1016/j.celrep.2022.111970","title":"Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging","abstract":"Protein quality control is important for healthy aging and is dysregulated in age-related diseases. The autophagy-lysosome and ubiquitin-proteasome are key for proteostasis, but it remains largely unknown whether other proteolytic systems also contribute to maintain proteostasis during aging. Here, we find that expression of proteolytic enzymes (proteases/peptidases) distinct from the autophagy-lysosome and ubiquitin-proteasome systems declines during skeletal muscle aging in Drosophila. Age-dependent protease downregulation undermines proteostasis, as demonstrated by the increase in detergent-insoluble poly-ubiquitinated proteins and pathogenic huntingtin-polyQ levels in response to protease knockdown. Computational analyses identify the transcription factor Ptx1 (homologous to human PITX1/2/3) as a regulator of protease expression. Consistent with this model, Ptx1 protein levels increase with aging, and Ptx1 RNAi counteracts the age-associated downregulation of protease expression. Moreover, Ptx1 RNAi improves muscle protein quality control in a protease-dependent manner and extends lifespan. These findings indicate that proteases and their transcriptional modulator Ptx1 ensure proteostasis during aging.","journal":"Cell Reports","year":2023,"id":333586,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"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":665900,"name":"Michelle Curley","orcid":"0000-0002-1746-1474","position":1,"is_corresponding":false},{"id":651020,"name":"Flávia A. Graça","orcid":"0000-0002-7342-6534","position":2,"is_corresponding":false},{"id":1061361,"name":"Maricela Robles‐Murguia","orcid":"0000-0002-1216-8930","position":3,"is_corresponding":false},{"id":55238,"name":"Abbas Shirinifard","orcid":"0000-0002-4517-6080","position":4,"is_corresponding":false},{"id":356183,"name":"David Finkelstein","orcid":"0000-0002-5196-6556","position":5,"is_corresponding":false},{"id":267013,"name":"Beisi Xu","orcid":"0000-0003-0099-858X","position":6,"is_corresponding":false},{"id":250676,"name":"Yiping Fan","orcid":"0000-0002-8430-4620","position":7,"is_corresponding":false},{"id":647469,"name":"Fabio Demontis","orcid":"0000-0002-8698-9555","position":8,"is_corresponding":false},{"id":667011,"name":"Jianqin Jiao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T01:09:44.297718Z","pmid":"36640359","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":[]}