Abstract
Aging is a complex biological process characterized by the accumulation of senescent cells that adopt a senescence-associated secretory phenotype (SASP), releasing proinflammatory mediators that drive tissue dysfunction and the onset of age-related diseases. Targeting cellular senescence has emerged as a novel therapeutic paradigm in geroscience. This review synthesizes recent preclinical and early clinical evidence on two innovative anti-aging strategies, senolytics and senomorphics, drawing from studies published in the last decade. The analysis focuses on mechanisms of action, therapeutic efficacy, limitations, and translational potential. Senolytics, including dasatinib–quercetin (D+Q) 263), natural compounds such as fisetin, selectively eliminate senescent cells by disrupting anti-apoptotic pathways. Senomorphics, such as rapamycin (mTOR inhibition) and ruxolitinib (JAK inhibition), suppress detrimental SASP components while preserving beneficial senescence functions. Both approaches demonstrate promise in extending healthspan and alleviating age-associated pathologies including fibrosis, neurodegeneration, and metabolic disorders. However, challenges persist, including limited specificity, off-target effects, and the absence of standardized biomarkers for patient selection and treatment monitoring. Senolytic and senomorphic therapies represent a rapidly advancing frontier in anti-aging research with substantial potential to improve healthy lifespan. Future progress will require the integration of combination strategies, precision medicine approaches informed by biomarkers, and advanced drug delivery technologies to enhance efficacy and safety.