Integrative Biomedical Research
Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326
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Volume 10 Number 1 2026
REVIEWS (Open Access)
Senescent Cell Heterogeneity and Precision Clearance Strategies: From Molecular Mechanism to Clinical Translation
Ragini Patel 1*, Yogendra Sahu 2
Integrative Biomedical Research 10 (1) 1-8 https://doi.org/10.25163/biomedical.10110880
Submitted: 04 November 2025 Revised: 20 December 2025 Accepted: 01 January 2026 Published: 03 January 2026
Abstract
Cellular senescence, an essentially irreversible growth arrest first described in cultured fibroblasts, is now recognized as a druggable driver of multiple age-related diseases, yet clinical progress has been slowed by the marked heterogeneity of senescent cells across tissues, inducing stressors, and disease states. We conducted a structured narrative synthesis of peer-reviewed literature senescence biology, single-cell senotyping, and senotherapeutic development, following informed search and appraisal strategy across PubMed/MEDLINE, Scopus, and Web of Science. Sixty-plus primary and review sources were synthesized into four evidence tables spanning first-generation agents, precision platforms, multi-tissue biomarkers, and human trials. First-generation senolytics (dasatinib plus quercetin, fisetin, navitoclax) demonstrate proof-of-concept efficacy but are constrained by dose-limiting toxicities, whereas next-generation platforms—PROTAC degraders, uPAR-directed CAR-T cells, senolytic vaccines, and galactose-caged prodrugs—achieve markedly higher predicted selectivity with lower off-target risk, operating through convergent mechanistic nodes upstream of tissue-level inflammaging. Early-phase human trials corroborate target engagement but remain underpowered for definitive efficacy claims. Precision senotherapy is mechanistically justified and clinically nascent; its translational success will depend on resolving the biomarker bottleneck and matching senotype-specific vulnerabilities to intervention class.
Keywords: cellular senescence; senolytics; senomorphics; SASP; single-cell senotyping; precision senotherapy; healthspan
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