Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction.

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.

SUBMITTER: Amor C 

PROVIDER: S-EPMC10950785 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature