Pharmacological frontiers in senescence: Transforming senescence with drug repurposing

Abstract

Repurposing conventional drugs as senotherapeutics offers a pragmatic and efficient approach to targeting cellular senescence, a key driver of aging-related diseases. Instead of relying solely on novel drug development, repurposing allows for the use of existing drugs with well-characterized pharmacokinetics, safety profiles, and clinical data, thereby accelerating their translation into senescence-targeted interventions. This chapter provides a comprehensive classification of senotherapeutics into senolytics, senomorphics, senoblockers, and senoreversers, detailing their mechanisms of action, molecular targets, and therapeutic applications. By categorizing these conventional agents based on their functional roles, this chapter presents a structured framework for understanding the pharmacological landscape of senotherapeutics. Additionally, this chapter discusses tissue-specific targeting, optimizing the dosing strategy to enhance the precision and safety of repurposed senotherapeutics. This chapter offers a systematic evaluation of drug repurposing, bridges the gap between preclinical and clinical applications, addressing both opportunities and challenges in repurposing the drugs. Eventually, this approach holds the potential to extend healthspan, mitigate age-related dysfunction, and provide more accessible and effective therapeutic options for disorders associated with cellular senescence.

Keywords: Clinical trials; Drug repurposing; Optimizing dosing strategies; Pharmacological approaches.