Steven Januar Kusmanto
Cellular senescence is an irreversible cell cycle arrest, triggered by stressors like telomere shortening, DNA damage, and oncogenic signaling. These cells, often referred to as 'zombie cells' because they cease dividing yet resist apoptosis, drive the Senescence-Associated Secretory Phenotype (SASP), releasing pro-inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While senescence is a protective mechanism against malignant proliferation, its persistence in tissues contributes to aging and age-related diseases (inflammaging). Recognizing this dual role forms the basis for developing therapies that bridge anti-aging, regenerative medicine, and oncology, as precise molecular regulatory mechanisms remain incompletely understood. This review interrelates these disciplines, focusing on targeted interventions against senescent cells (SnCs). These interventions include senolytics (agents that selectively eliminate SnCs) and senomorphics (agents that suppress the SASP), offering translational insights from anti-aging/aesthetic applications into integrated treatment models. The framework addresses cancer therapeutics via immunologic modalities such as monoclonal antibodies (mAbs) and CAR T-cell therapy, alongside nucleic acid-based therapeutics (mRNA and siRNA), and is used in combination with broad-spectrum therapeutics. The novelty lies in synthesizing these disparate fields, unified by cellular senescence as a central mechanistic target. Ultimately, the goal is to identify targets that induce tumor regression, mitigate age-related vulnerabilities, promote tissue homeostasis and regeneration, and improve quality of life and overall survival.