{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Amor C"],"funding":["NIA NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["336-349"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10950785"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(3)"],"pubmed_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."],"journal":["Nature aging"],"pubmed_title":["Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction."],"pmcid":["PMC10950785"],"funding_grant_id":["R01 AG082800","P30 CA008748","R01 CA190092","U01 CA224013","DP5 OD033055","R01 AG065396","P30 CA045508","U01 AG077925","R01 CA188134","S10 OD028632","U01 CA210240","R35 CA197594","R01 CA229699"],"pubmed_authors":["Boyer JA","Ho YJ","Graham C","Mezzadra R","Levine RL","Chowdhury S","Sadelain M","Wereski MG","Amor C","Lowe SW","Tuveson DA","Fernandez-Maestre I","Feucht J","Jones LW","Nadella S","Nnuji-John E","Carrasco SE","Barthet VJA","Hinterleitner C"],"additional_accession":[]},"is_claimable":false,"name":"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2024-11-15T04:14:53.73Z","creation":"2024-11-15T04:14:53.73Z"},"accession":"S-EPMC10950785","cross_references":{"pubmed":["38267706"],"doi":["10.1038/s43587-023-00560-5"]}}