Cleaning, Chasing and Calming: Promising Paradigms of Senotherapy in Aging-Related Diseases

With the acceleration of global population aging, the pathological accumulation of senescent cells (SnCs) has been confirmed as the core biological mechanism driving multiple aging-related diseases. This article aims to systematically review the formation mechanism of SnCs and their pathological roles in various tissue lesions, and to specifically evaluate the progress of three cutting-edge intervention strategies (Senolytics, Immuno-senolytics and Senomorphics). Senolytics selectively induces programmed apoptosis in SnCs by antagonizing senescent cell anti-apoptotic pathways. Immuno-senolytics include vaccines, engineered cell therapy and specific antibodies, which utilize the immune surveillance mechanism to achieve efficient elimination of SnCs. Senomorphics precisely reshape the SASP profile by targeting signaling axis or interfering with epigenetic modifications. Although the strategies have demonstrated remarkable potential for reversing pathology, their clinical translation still faces challenges such as the heterogeneity of SnCs, the lack of specific markers, and potential off-target toxicity. Future research should focus on multidisciplinary collaboration, aiming to optimize spatiotemporal targeted delivery systems and combination drug regimens to build a safer and more precise anti-senescence treatment system.