SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights

Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, and tumorigenesis. This review examines SASP’s molecular regulation, dual roles in health and pathology, and therapeutic potential. The following two main strategies are explored: senescence clearance, which eliminates SASP-producing cells, and SASP modulation, which refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, and cGAS-STING, are discussed alongside pharmacological, immunotherapeutic, gene-editing, and epigenetic interventions. SASP heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, and ethical considerations. SASP modulation emerges as a promising strategy for aging, oncology, and tissue repair, with future advancements relying on multi-omics and AI-driven insights to optimize clinical outcomes.