Cellular senescence, a fundamental hallmark of aging, plays a dual role in both tumor suppression and the pathogenesis of age-related diseases. For instance, the accumulation of senescent cells drives a chronic, low-grade inflammatory state known as inflammaging, which is a key contributor to tissue dysfunction and disease. This pattern is characterized by a unique secretory profile known as the Senescence-Associated Secretory Phenotype (SASP), which indicates a state of organismal aging, tissue degeneration, and the secretion of pro-inflammatory cytokines, chemokines, growth factors, and extracellular matrix remodeling enzymes in the cellular microenvironment. However, the precise molecular mechanisms that regulate senescence and its escape remain incompletely understood, limiting the development of targeted therapeutic strategies. Recent developments in senescence research have identified compelling therapeutic targets, ranging from an-ti-neoplastic interventions to the establishment of integrated treatment models for both regenerative and aesthetic treatments. This review reveals the mechanistic underpin-nings that interrelate these seemingly disparate disciplines, demonstrating how targeted interventions against senescent cells, including senolytics (agents that selectively elim-inate senescent cells) and senomorphics (agents that suppress the detrimental aspects of the SASP), utilized in anti-aging and aesthetic applications, provide valuable translational insights for regenerative medicine and oncology. This framework addresses cancer therapeutics through immunologic modalities, including monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T-cell therapy, alongside nucleic acid-based ther-apeutics such as messenger RNA (mRNA) and small interfering RNA (siRNA), poten-tially in conjunction with senotherapeutics (a broad term encompassing senolytics and senomorphics). The novelty of this work lies in its synthesis of perspectives from seemingly unrelated fields unified by cellular senescence as a central mechanistic treatment target. Ultimately, the goal is to identify potential therapeutic targets that induce tumor regression, mitigate age-related vulnerabilities, and promote tissue ho-meostasis and regeneration, leading to improved patient-reported outcomes and en-hanced overall survival.
Steven Januar Kusmanto (Tue,) studied this question.