Mitophagy Enhancement Delays Mouse Mesenchymal Stem Cell Senescence by Attenuating the Senescence-Associated Secretory Phenotype.

Abstract

Aging is a complex biological process that heightens susceptibility to age-related diseases, often driven by declining mitochondrial function. Mitophagy, the selective removal of damaged mitochondria, is a key quality-control mechanism essential for maintaining cellular health, and its decline has been closely linked to aging. However, the specific role of mitophagy in cellular senescence, a hallmark of aging, remains insufficiently understood, largely due to the lack of methods to manipulate mitophagy. In this study, we employed UMI-77, a new potent mitophagy activator, to evaluate its effects on senescence in mouse mesenchymal stem cells (MSCs). Our results show that UMI-77 preserves mitochondrial integrity and effectively delays cellular senescence through mitophagy. Mechanistically, UMI-77 markedly suppressed the senescence-associated secretory phenotype (SASP). Together, our findings reveal a new anti-aging therapeutic application for UMI-77 by targeting senescence-associated chronic inflammation through mitophagy induction and SASP reduction.