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study evaluates senolytic CAR T-cell therapy targeting uPAR-positive cells in aged mice, showing its effectiveness in mitigating age-related metabolic dysfunction and offering a potential long-lasting treatment for aging-associated conditions.
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Cellular senescence is an irreversible cell cycle arrest induced in response to stress. Under stressful conditions, matrix remodeling enzymes and pro-inflammatory cytokines are produced, termed Senescence-Associated Secretory Phenotype (SASP). In young individuals with physiological conditions, such as tumor suppression and wound healing, SASP facilitates the recruitment of immune cells, which facilitate tissue restoration and the elimination of senescent cells. In the elderly, senescent cells accumulate due to reduced immune system function and increased tissue damage. To date, most senescent therapies include small-molecule drugs that require repeated administration and poorly target the affected area. A recent study in Nature Aging evaluates the efficacy of a senolytic therapy based on CAR-T cells. This therapy targets urokinase plasminogen activator receptor (uPAR)-positive cells, which accumulate during aging. In this study, senolytic cell therapies were shown to alleviate symptoms associated with physiological aging, including metabolic dysfunction.