Cellular senescence is a fundamental biological process that plays a complex role in human health and disease. While senescence initially serves as a protective mechanism against uncontrolled cell proliferation, the persistent accumulation of senescent cells can contribute to chronic inflammation, tissue dysfunction, and disease progression. Growing evidence has linked cellular senescence to a wide range of conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic dysfunction, and cancer. These findings have positioned senescence as a promising therapeutic target. However, effectively targeting senescent cells while minimizing damage to healthy tissues remains a major challenge, highlighting the need for more precise and controllable therapeutic strategies.
Recently, a comprehensive review titled "Modulating senescence for therapeutic delivery" was published in Med-X . The review systematically examines the relationship between cellular senescence and disease progression, summarizes current therapeutic approaches for modulating senescence, and highlights emerging drug delivery technologies designed to improve treatment specificity, safety, and efficacy. By integrating advances in pharmaceutical sciences, nanotechnology, and molecular biology, the review provides new perspectives on developing targeted therapies for senescence-associated diseases.
1. Cellular Senescence: A Double-Edged Sword in Disease Progression
Cellular senescence is characterized by permanent cell cycle arrest, accompanied by changes in cellular morphology, metabolism, and gene regulation. One of its defining features is the senescence-associated secretory phenotype (SASP), through which senescent cells release inflammatory cytokines, growth factors, and other signaling molecules that influence surrounding tissues. Although senescence can suppress abnormal cell proliferation and protect against tumor formation, the prolonged accumulation of senescent cells may promote chronic inflammation and tissue deterioration. These effects contribute to the development of multiple age-related diseases, including atherosclerosis, neurodegeneration, diabetes, pulmonary fibrosis, and osteoporosis. In cancer, therapy-induced senescence can initially inhibit tumor growth but may subsequently promote treatment resistance and recurrence through SASP-mediated remodeling of the tumor microenvironment. This dual role underscores the importance of precisely regulating senescence rather than indiscriminately eliminating senescent cells.
2. Senescence-Modulating Therapies: Current Strategies and Limitations
Based on the growing understanding of senescence-associated disease mechanisms, two major therapeutic approaches have emerged: senolytics and senomorphics. Senolytics, including navitoclax, dasatinib, and quercetin, aim to selectively eliminate senescent cells by disrupting their survival pathways. In contrast, senomorphics, such as rapamycin and metformin, primarily suppress harmful SASP signaling without directly inducing senescent cell death. Although these strategies have demonstrated promising therapeutic effects in preclinical studies, their broader clinical application remains limited by insufficient targeting specificity, poor pharmacokinetic properties, and potential off-target toxicity. These challenges highlight the importance of developing advanced delivery technologies that can improve drug accumulation at disease sites while enabling more controlled therapeutic intervention.
3. Advanced Drug Delivery Systems: Enabling Precise Senescence Modulation
To overcome the limitations of conventional senotherapeutics, researchers are increasingly exploring advanced drug delivery systems that integrate targeted delivery, controlled release, and improved therapeutic selectivity. Polymer-based nanocarriers can enhance drug stability and enable sustained release, while lipid-based systems, including functionalized liposomes and nanoparticles, facilitate targeted delivery to senescent tissues. For example, bone-targeted liposomes have been investigated for eliminating senescent cells associated with osteoporosis, whereas receptor-targeted nanoparticles have shown potential for clearing therapy-induced senescent tumor cells. Beyond conventional nanocarriers, stimuli-responsive nano-assembled systems can exploit senescence-associated biomarkers, such as β-galactosidase, to activate therapeutic agents selectively. Emerging cell-based approaches, including engineered extracellular vesicles and chimeric antigen receptor (CAR) T cells, further expand the possibilities for targeting senescent cell populations. Together, these technologies offer promising strategies for improving the precision and therapeutic effectiveness of senescence modulation.
4. Cell-Based Delivery Systems: Harnessing Biological Platforms for Senescence Targeting
Beyond conventional nanocarriers, cell-based delivery systems offer promising approaches for targeted senescence modulation. Engineered extracellular vesicles (EVs) can deliver therapeutic agents to senescent cells, potentially improving treatment specificity and efficacy. Meanwhile, chimeric antigen receptor (CAR) T cells can recognize senescence-associated markers, such as NKG2D ligands and uPAR, to selectively eliminate senescent cells. Recent advances in lipid nanoparticle-mediated RNA delivery further enable the generation of senescence-targeting CAR-T cells in vivo. Together, these strategies highlight the potential of integrating cellular engineering and targeted delivery for more precise senescence therapies.
5. Scholarly Value and Future Perspectives
This review highlights the growing potential of integrating senescence biology with advanced drug delivery technologies, ranging from polymeric and lipid-based nanocarriers to engineered extracellular vesicles and cell-based therapies. These approaches offer opportunities to improve therapeutic targeting, control drug release, and reduce off-target toxicity. Future progress will require a deeper understanding of senescent cell heterogeneity, more reliable targeting biomarkers, and rigorous evaluation of therapeutic safety and efficacy. By bridging fundamental senescence mechanisms with innovations in nanomedicine and cellular engineering, the review outlines promising directions for developing more precise and clinically applicable therapies for age-related diseases and cancer.
Med-X
News article
Modulating senescence for therapeutic delivery
7-Sep-2026