{"doi":"10.1101/2020.06.04.135087","title":"Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness","abstract":"Summary From age 65 onwards, the risk of cancer incidence and associated mortality is substantially higher 1-3 . Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy 4 . For decades, the link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the well-established role of diet, exercise and small molecules that target the pace of metabolic aging 5-8 . Here, we show that metabolic alterations that occur with age can render a systemic environment favorable to progression and aggressiveness of tumors. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is significantly up-regulated in the serum of older people, and functions as a mediator of tumor progression. We traced this to the induction of SOX4 and a consequent transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, accumulation of MMA represents a novel link between aging and cancer progression, implicating MMA as a novel therapeutic target for advanced carcinomas.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126877,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":574892,"name":"Didem Ilter","orcid":"0000-0001-7506-8198","position":1,"is_corresponding":false},{"id":426223,"name":"Vivien Low","orcid":"0000-0002-8561-011X","position":2,"is_corresponding":false},{"id":574893,"name":"Jennifer E. Endress","orcid":"0000-0002-7538-6302","position":3,"is_corresponding":false},{"id":109847,"name":"Juan Fernández-García","orcid":"0000-0003-3422-3627","position":4,"is_corresponding":false},{"id":574894,"name":"Adam Rosenzweig","orcid":"0009-0001-4059-9471","position":5,"is_corresponding":false},{"id":575385,"name":"Tanya Schild","orcid":null,"position":6,"is_corresponding":false},{"id":273618,"name":"Dorien Broekaert","orcid":"0000-0002-9777-1607","position":7,"is_corresponding":false},{"id":574895,"name":"Adnan Ahmed","orcid":"0000-0002-1883-7680","position":8,"is_corresponding":false},{"id":273620,"name":"Mélanie Planque","orcid":"0000-0001-7052-7084","position":9,"is_corresponding":false},{"id":574896,"name":"Ilaria Elia","orcid":"0000-0003-0922-9429","position":10,"is_corresponding":false},{"id":472692,"name":"Julie Han","orcid":"0000-0002-5938-3734","position":11,"is_corresponding":false},{"id":574897,"name":"Charles G. Kinzig","orcid":"0000-0002-4592-7411","position":12,"is_corresponding":false},{"id":293814,"name":"Edouard Mullarky","orcid":null,"position":13,"is_corresponding":false},{"id":295482,"name":"Anders P. Mutvei","orcid":"0000-0002-2498-5225","position":14,"is_corresponding":false},{"id":3257,"name":"John M. Asara","orcid":"0000-0001-7450-2589","position":15,"is_corresponding":false},{"id":258549,"name":"Rafael de Cabo","orcid":"0000-0003-2830-5693","position":16,"is_corresponding":false},{"id":51785,"name":"Lewis C. Cantley","orcid":"0000-0002-1298-7653","position":17,"is_corresponding":false},{"id":259321,"name":"Noah Dephoure","orcid":"0000-0001-5802-2657","position":18,"is_corresponding":false},{"id":109854,"name":"Sarah‐Maria Fendt","orcid":"0000-0001-6018-9296","position":19,"is_corresponding":false},{"id":85690,"name":"John Blenis","orcid":"0000-0003-3622-2337","position":20,"is_corresponding":false},{"id":426224,"name":"Ana P. Gomes","orcid":"0000-0003-0881-727X","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}