{"doi":"10.1101/2023.06.16.545146","title":"Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging","abstract":"Abstract Declines in mitochondrial content and impaired cytochrome c oxidase activity (complex IV) can result in reduced energy metabolism and increased levels of oxidants. Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species (ROS) within cells. To investigate the effect of acute and long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 (L5) in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":408867,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":1188704,"name":"Dorra Frikha-Benayed","orcid":null,"position":1,"is_corresponding":false},{"id":318600,"name":"Ryan Richard Ruff","orcid":"0000-0003-0731-5614","position":2,"is_corresponding":false},{"id":391347,"name":"Gozde Yildirim","orcid":"0000-0002-0127-7728","position":3,"is_corresponding":false},{"id":320885,"name":"Manisha Dixit","orcid":"0000-0001-6350-4677","position":4,"is_corresponding":false},{"id":416009,"name":"Ron Korstanje","orcid":"0000-0002-2808-1610","position":5,"is_corresponding":false},{"id":290115,"name":"Laura Robinson","orcid":null,"position":6,"is_corresponding":false},{"id":97735,"name":"Richard A. Miller","orcid":"0000-0001-9266-9649","position":7,"is_corresponding":false},{"id":195157,"name":"David Harrison","orcid":null,"position":8,"is_corresponding":false},{"id":268618,"name":"Randy Strong","orcid":"0000-0001-6643-3288","position":9,"is_corresponding":false},{"id":391348,"name":"Mitchell B. Schaffler","orcid":"0000-0001-5780-7073","position":10,"is_corresponding":false},{"id":320890,"name":"Shoshana Yakar","orcid":"0000-0002-2352-1330","position":11,"is_corresponding":false},{"id":320884,"name":"Sher Bahadur Poudel","orcid":"0000-0003-3733-4648","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:21:22.368387Z","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":[]}