{"id":"doi:10.1038/s43587-023-00560-5","kind":"article","title":"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction","authors":["Amor C","Fernández-Maestre I","Chowdhury S","Ho YJ","Nadella S","Graham C","Carrasco SE","Nnuji-John E","Feucht J","Hinterleitner C","Barthet VJA","Boyer JA","Mezzadra R","Wereski MG","Tuveson DA","Levine RL","Jones LW","Sadelain M","Lowe SW"],"author_count":19,"year":2024,"published":"2024-01-24","venue":"Nature aging","cited_by":200,"doi":"10.1038/s43587-023-00560-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s43587-023-00560-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s43587-023-00560-5","updated":null,"pmid":"38267706","pmcid":"PMC10950785","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10950785/pdf","abstract":"Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction\" by Amor C, Fernández-Maestre I, Chowdhury S et al., https://doi.org/10.1038/s43587-023-00560-5, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}