Chimeric Antigen Receptor T Cells as Living Therapeutics Targeting Senescence and Age-Related Diseases

The aging of the global population exacerbates the burden of age-related diseases; however, therapies that can intervene in fundamental aging processes are lacking. Senescent cells drive chronic inflammation and multitissue dysfunction through the secretion of proinflammatory and profibrotic senescence-associated secretory phenotype cells, making them emerging therapeutic targets. Although first-generation senolytic drugs have entered clinical trials, they face limitations such as insufficient targeting specificity and transient efficacy. The success of chimeric antigen receptor T cell (CAR T cell) therapy in cancer immunotherapy has validated its precision clearance capabilities as a "living drug". This review systematically elaborates on the paradigm shift of extending CAR T cell therapy to aging medicine, from the discovery and validation of surface targets on senescent cells to a CAR engineering design tailored to the senescent microenvironment and from evidence of reversing fibrosis and improving metabolic function in preclinical models to the challenges of specificity, safety, and manufacturing faced in clinical translation. Finally, future directions for integrating technologies such as mRNA delivery and artificial intelligence are envisioned in this article, which proposes that CAR T cell therapy may drive the evolution of medicine from "treating single diseases" to "intervening in shared aging processes", offering transformative strategies to achieve healthy aging.