Insights into targeting cellular senescence with senolytic therapy: The journey from preclinical trials to clinical practice

• Published in: Mechanisms of ageing and development 2024-04, Vol.218, p.111918-111918, Article 111918
• Main Authors: Chen, Peng, Wang, Yulai, Zhou, Benhong
• Format: Article
• Language: English
• Subjects: Cellular senescence; Clinical application; Drug screening; Senescence-associated secretory phenotype; Senolytics
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2024.111918

Interconnected, fundamental aging processes are central to many illnesses and diseases. Cellular senescence is a mechanism that halts the cell cycle in response to harmful stimuli. Senescent cells (SnCs) can emerge at any point in life, and their persistence, along with the numerous proteins they secrete, can negatively affect tissue function. Interventions aimed at combating persistent SnCs, which can destroy tissues, have been used in preclinical models to delay, halt, or even reverse various diseases. Consequently, the development of small-molecule senolytic medicines designed to specifically eliminate SnCs has opened potential avenues for the prevention or treatment of multiple diseases and age-related issues in humans. In this review, we explore the most promising approaches for translating small-molecule senolytics and other interventions targeting senescence in clinical practice. This discussion highlights the rationale for considering SnCs as therapeutic targets for diseases affecting individuals of all ages. •Gerodiagnostics and cell morphology are reliable and sensitive biomarkers of SnCs, and can help to quantify SnCs abundance, the SASP and senolysis as well as other pillars of aging.•Randomized controlled trials will define the safety and potential benefits of senolytic strategies, scientific and regulatory challenges must be addressed in the near term if senolytics are to be used in the clinic.•Spatial transcriptomics, spatial epigenomics, spatial metabolomics, and hPSC-derived of models of aging organoids can be applied to study the molecular mechanism of cellular senescence.