Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions

Cellular senescence is a fundamental mechanism in aging, marked by irreversible growth arrest and diverse functional changes, including, but not limited to, the development of a senescence-associated secretory phenotype (SASP). While transient senescence contributes to beneficial processes such as tissue repair and tumor suppression, the persistent accumulation of senescent cells is implicated in tissue dysfunction, chronic inflammation, and age-related diseases. Notably, the SASP can exert both pro-inflammatory and immunosuppressive effects, depending on cell type, tissue context, and temporal dynamics, particularly in early stages where it may be profibrotic and immunomodulatory. Recent advances in senotherapeutics have led to two principal strategies for targeting senescent cells: senolytics, which selectively induce their apoptosis, and senomorphics, which modulate deleterious aspects of the senescence phenotype, including the SASP, without removing the cells. This review critically examines the molecular mechanisms, therapeutic agents, and clinical potential of both approaches in the context of anti-aging interventions. We discuss major classes of senolytics, such as tyrosine kinase inhibitors, BCL-2 family inhibitors, and natural polyphenols, alongside senomorphics including mTOR and JAK inhibitors, rapalogs, and epigenetic modulators. Additionally, we explore the biological heterogeneity of senescent cells, challenges in developing specific biomarkers, and the dualistic role of senescence in physiological versus pathological states. The review also highlights emerging tools, such as targeted delivery systems, multi-omics integration, and AI-assisted drug discovery, which are advancing precision geroscience and shaping future anti-aging strategies.