A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

Abstract

Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.