Senescence Modulation: An Applied Science Review of Strategies in Anti-Aging, Regenerative Aesthetics, and Oncology Therapy

Cellular senescence is an irreversible state of cell cycle arrest that occurs in response to various stressors, including telomere shortening, DNA damage, and oncogenic signaling. These changes transform a cell into a source of pro-inflammatory and pro-degeneration signals (through pro-inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes), leading to the Senescence-Associated Secretory Phenotype (SASP) within the cellular microenvironment. Senescence serves as a protective mechanism against the proliferation of damaged or potentially malignant cells, but its persistence in tissues is understood to contribute to aging and age-related diseases (inflammaging). Recognizing the dual role of senescence—as both a safeguard against damaged cell proliferation and a driver of tissue degeneration—forms the foundation for developing therapies that bridge anti-aging, regenerative medicine, and oncology. The precise molecular mechanisms that regulate senescence and its escape are incompletely understood, which limits the development of targeted therapeutic strategies. Recent developments in senescence research have identified compelling therapeutic targets, ranging from anti-neoplastic interventions to the establishment of integrated treatment models for both regenerative and aesthetic treatments. This review reveals the mechanistic underpinnings that interrelate these seemingly disparate disciplines, demonstrating how targeted interventions against senescent cells (SnCs), including senolytics (agents that selectively eliminate SnCs) and senomorphics (agents that suppress the detrimental aspects of the SASP), utilized in anti-aging and aesthetic applications, provide valuable translational insights for developing integrated treatment models in 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 therapeutics such as messenger RNA (mRNA) and small interfering RNA (siRNA), potentially 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 homeostasis and regeneration, leading to improved patient-reported outcomes and enhanced overall survival.