Cellular senescence in neurodegenerative diseases: A bibliometric analysis and mechanistic synthesis linking translational pathways to therapeutic implications

BACKGROUND: Cellular senescence is now recognized as a pivotal driver of neurodegenerative diseases (NDs). Despite advances in understanding senescence mechanisms, such as the p16INK4A/p53-p21CIP1 pathways and the senescence-associated secretory phenotype (SASP), along with the development of therapeutic strategies like senotherapeutics, the research landscape remains fragmented. OBJECTIVE: Systematically addresses the fragmentation characterizing current research on cellular senescence in NDs, integrating bibliometric analysis with a mechanistic synthesis of translational relevance and therapeutic implications. METHODS: A comprehensive bibliometric analysis was performed. Literature retrieval on cellular senescence and four NDs (AD, PD, ALS, HD) was executed in Web of Science Core Collection (WoSCC) on April 30, 2025. CiteSpace V.6.4 R1 and VOSviewer 1.6.20 reconstructed networks for temporal trends, burst detection, and co-occurrence visualization. In addition to bibliometric mapping, we provide a mechanistic synthesis of emerging translational pathways. RESULTS: Analysis included 269 relevant articles (2002-April 2025). Annual publications and cumulative citations increased markedly since 2018. The US led in output/influence, followed by China and Italy. Key collaborative institutions included Chinese Academy of Sciences, University of Texas System, and University of California System. Leading authors were Lorenz Studer, Judith Campisi, and Julie K. Andersen. Tyler J. Bussian and Peisu Zhang were highly co-cited. Top-cited journals were Nature, PNAS, and PLOS One. Research hotspots focus on abnormal tau protein in senescence and senescent microglia mediating chronic neuroinflammation, development of multi-target senomorphics targeting SASP is emerging as a promising therapeutic direction. CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.