Senolytics and Senomorphics: Pharmacological Targeting of Cellular Senescence in Brain Aging and Neurodegeneration

Cellular senescence has emerged as an important biological process in brain aging and neurodegeneration. Senescent cells are characterized by stable cell-cycle arrest and persistent metabolic activity, accompanied by the secretion of pro-inflammatory cytokines, chemokines, and matrix-remodeling factors known as the senescence-associated secretory phenotype (SASP). In the central nervous system, this chronic inflammatory state may impair neuronal and glial function, disturb tissue homeostasis, and promote pathological progression in disorders such as Alzheimer’s disease, Parkinson’s disease, tauopathies, and age-related cognitive decline. Geroscience has introduced a new therapeutic framework by proposing that targeting fundamental aging mechanisms may modify multiple disorders simultaneously. Within this context, senolytics and senomorphics have attracted increasing attention as pharmacological approaches to eliminate senescent cells or suppress their harmful secretory phenotype.This Research Topic aims to provide a focused platform for advances in the pharmacological targeting of cellular senescence in brain aging and neurodegenerative disease. It seeks to integrate basic, translational, and clinical studies that clarify how senescence develops in distinct brain cell populations, how it contributes to neuroinflammation and tissue dysfunction, and how senolytic or senomorphic interventions may alter disease trajectories. We particularly welcome work addressing unresolved questions in the field, including the reliable identification of senescent cells in vivo, the heterogeneity of senescence programs across neuronal and glial cell types, the central nervous system penetrance and selectivity of candidate compounds, optimal treatment windows, and safety considerations in aged or diseased populations. The Topic also aims to stimulate discussion on biomarker development, patient stratification, combination therapies, and the integration of senescence-targeted strategies with existing disease-modifying approaches. Overall, the goal is to accelerate mechanistic understanding and therapeutic translation in this rapidly developing area.This Research Topic welcomes original research articles, reviews, mini-reviews, perspectives, and clinical or translational studies related to senescence-targeted pharmacology in the central nervous system. Topics of interest include:- mechanisms of neuronal and glial senescence; - biomarkers and cell-type-specific SASP signatures; - pharmacology, selectivity, blood-brain barrier penetrance, and safety of senolytics; - senomorphic approaches that suppress SASP signaling;- links between senescence, autophagy, and proteostasis; - the role of senescence in Alzheimer’s disease, Parkinson’s disease, tauopathies, and cognitive aging. Submissions on translational biomarkers, imaging, cerebrospinal fluid or blood-based indicators, early-phase clinical studies, real-world evidence, sex differences, genetic modifiers such as APOE, and rational combination therapies are particularly encouraged. Studies should provide clear mechanistic, pharmacological, translational, or clinical relevance to brain aging and neurodegeneration. Topic editors: Peng Xu, Minghui Wang, Aiqun Li, Chen Ming Source: https://www.frontiersin.org/research-topics/81166/senolytics-and-senomorphics-pharmacological-targeting-of-cellular-senescence-in-brain-aging-and-neurodegeneration