Senotherapy: scientific advances and clinical potential of senolytic therapies

Senotherapy represents an emerging therapeutic approach to combat deleterious senescent cells, whose pro-inflammatory accumulation contributes to various aging-associated pathologies. This study aimed to analyze and systematize recent scientific advances in senotherapy, with emphasis on senolytic therapies, their innovations, and clinical potential. An integrative literature review was conducted covering the period from January 2019 to June 2025, carried out across four databases: SciELO, PubMed, ScienceDirect, and Web of Science, following PRISMA 2020 guidelines for the identification, screening, eligibility, and inclusion stages. Fifteen articles were selected from a total of 113 identified publications, with a predominance of preclinical evidence (13 of the 15 studies were restricted to in vitro or in vivo designs) and only two compounds referenced in preliminary clinical trials. The results evidence a rapidly expanding field, with a peak of scientific productivity in 2024, revealing that senolytic therapies predominantly target the modulation of anti-apoptotic pathways – such as the Bcl-2 protein family and the PI3K/AKT/mTOR(definition) pathway. Agents such as the dasatinib and quercetin combination, fisetin, and navitoclax demonstrated preclinical efficacy in models of neurodegenerative diseases, metabolic disorders, musculoskeletal and cardiovascular conditions, and in stem cell preservation. However, significant challenges persist, including on-target toxicity (e.g., navitoclax-induced thrombocytopenia), contextual heterogeneity of response across tissues and age groups, and the absence of fully validated non-invasive biomarkers in all analyzed studies for quantifying the senescent burden and monitoring therapeutic efficacy. It is concluded that senotherapy represents a promising frontier, but its clinical consolidation requires articulated advances in safety, specificity, patient stratification, and standardization, in order to translate preclinical potential into effective applications in aging medicine.