cellular senescence

Overview

Cellular senescence is a stable cell-state program in which cells undergo essentially irreversible growth arrest while remaining metabolically active. It is widely recognized as a hallmark of aging and a contributor to age-related tissue dysfunction, but it also appears in diverse contexts such as oxidative stress, DNA damage, oncogenic signaling, radiotherapy, metabolic disease, and chronic inflammation. Senescent cells often develop a senescence-associated secretory phenotype (SASP), characterized by the release of proinflammatory cytokines, growth factors, and other mediators that can reshape the tissue microenvironment.

Biologically, cellular senescence has a dual role. It can act as a tumor-suppressive mechanism by preventing the proliferation of damaged cells, yet persistent senescent cells can promote tissue injury, fibrosis, immune dysregulation, and disease progression. Recent work has linked senescence to mitochondrial dysfunction, mitophagy defects, p53 signaling, Wnt/β-catenin pathway changes, FOXO1-related geroprotective pathways, and inflammatory remodeling in tissues such as skin, kidney, lung, bone, lens, and reproductive organs.

Focus of Latest Publications

Recent publications portray cellular senescence as a central process connecting aging biology with disease progression, biomarker discovery, and therapeutic targeting. A 2026 Cell study described cellular senescence as comprising diverse cell states emerging across human tissues during aging and disease, while a companion Cell Reports study emphasized that circulating senescence signatures may track distinct dimensions of health status and longitudinal trajectories in human cohorts. Together, these studies reinforce the idea that senescence is not a single uniform state, but a heterogeneous biological program with measurable systemic correlates.

Several studies focused on disease-specific roles of senescence. In sepsis, cellular senescence was described as a process that can exacerbate tissue damage and organ dysfunction, motivating bioinformatics and machine learning analyses to identify senescence-related genes and potential drugs. In diabetic kidney disease, senescence was presented as an irreversible cell-cycle arrest state that drives chronic inflammation and tissue damage, supporting senotherapeutic approaches and regenerative cell-based therapies. In chronic lung pathology, senescence was linked to organelle dysfunction in lung fibroblasts, with PEX5 implicated in integrating p38 MAPK signaling and taurine metabolism to regulate the senescent phenotype.

Cancer-related studies repeatedly connected senescence with the tumor microenvironment, immune regulation, and treatment response. In ovarian cancer, integrated single-cell sequencing and multi-omics analyses suggested that senescence influences immune-metabolic features and prognosis, including effects on the tumor microenvironment and metabolic status. In clear cell renal cell carcinoma, multi-omics and machine learning approaches investigated senescence levels and epithelial-endothelial crosstalk, with the targeting of senescent cells highlighted as a promising therapeutic strategy. In laryngeal squamous cell carcinoma, m6A-related senescence genes were explored as part of an undercharacterized regulatory landscape. In triple-negative breast cancer, an ultrasound-responsive biomimetic nanocarrier was reported to trigger coordinated apoptosis, ferroptosis, and senescence activation via p21/p16 signaling, amplifying immunogenic cell death in the setting of BRD4 degradation and sonodynamic therapy. Another radiotherapy-focused study reported that prophylactic sequential drug administration reduced lysosomal cholesterol deposition and cellular senescence, thereby enhancing radiosensitization and prolonging survival in mice.

Senescence was also examined in aging and degenerative contexts. In skeletal aging, it was described as a key mechanism in both physiological and accelerated conditions, including radiotherapy-associated damage. In bone repair, periosteal mitochondrial DNA structures were reported to drive aging-associated poor skeletal repair through mitophagy and cell senescence. In vascular aging, endothelial dysfunction and inflammageing were linked to an imbalance between protective autophagy and cellular senescence, with a proinflammatory SASP contributing to decline. In brain aging, senescence was discussed alongside autophagy as part of neurodegenerative disease biology, with intermittent fasting proposed as a neuroprotective context. In testicular aging, bleomycin induced a rapid and robust senescence response in a translational peritubular cell model, and in primate epididymal aging, FOXO1 deficiency was shown to drive cellular senescence in human epididymal epithelial cells.

Other studies addressed senescence in ocular, dermatologic, and stem-cell systems. In age-related cataract, RORA targeting PRNP modulated oxidative injury-induced senescence and apoptosis in lens epithelial cells, where inhibiting RORA alleviated senescence and improved resistance to oxidative stress. In human skin, GLP-1 receptor agonists were associated with reduced epidermal p21 expression in a pilot study, suggesting possible relevance to skin senescence and metabolic modulation. Transcriptomic profiling of chlorogenic acid and taurine in human skin cells also pointed to antioxidant compounds that may reduce skin cellular senescence. In human umbilical cord mesenchymal stem cells, deep learning-assisted nanomechanical evaluation identified a senescence-associated mechanical phenotype, indicating that senescence can be detected through biophysical changes as well as molecular markers.

Across these studies, senescence was repeatedly linked to mitochondrial homeostasis, oxidative stress, p53 signaling, FOXO1, sirtuin 1, PRKAA1, AKT serine/threonine kinase 1, mechanistic target of rapamycin kinase, and Wnt/β-catenin pathway modulation. The literature also highlighted senescence-associated inflammatory mediators such as Interleukin 1 beta and anti-inflammatory cytokines, as well as interactions with macrophages, cancer-associated fibroblasts, CAR-T cells, and CD8+ S100B+ T cells in the tumor immune microenvironment. Overall, the recent research context presents cellular senescence as both a biomarker-rich aging process and a tractable therapeutic target in cancer, fibrosis, metabolic disease, and degenerative disorders.

Key Publications

• Jun Single-cell Transcriptomics Reveals that the SORBS1/FBXO22/BAG3 Axis Drives Astrocyte Senescence via Calcium Signaling and Affects Alzheimer's Disease-Related Neuronal Damage. (Neuromolecular medicine, 2026, PMID 42307825): "ScRNA-seq analysis revealed a marked reduction in astrocyte expression in AD brains, which may result from cellular senescence."
• Jun Monoamine Oxidase A-Activatable Theranostic Probe for Image-Guided Photodynamic Elimination of Senescent Tumor Cells. (Analytical chemistry, 2026, PMID 42225351): "Cellular senescence contributes to tumor recurrence by fostering a pro-tumorigenic microenvironment after therapy."
• Jun Circulating cell type senescence signatures track distinct dimensions of health status and trajectories in human longitudinal cohorts. (Cell reports, 2026, PMID 42276069): "Cellular senescence is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential."
• Jun Charting human cellular senescence in aging and disease. (Cell, 2026, PMID 42276030): "Cellular senescence comprises diverse cell states emerging across human tissues during aging and disease."
• Jun HMGA2 identified via m6A-senescence multi-omics in laryngeal squamous cell carcinoma. (Scientific reports, 2026, PMID 42265324): "N6-methyladenosine (m6A) modification and cellular senescence have been individually implicated in tumor biology, but the landscape of m6A-related senescence genes in laryngeal squamous cell carcinoma (LSCC) remains underexplored."
• Jun The role of cellular senescence in immune-metabolic features and prognosis of ovarian cancer: an integrated analysis based on single-cell sequencing and multi-omics data. (GeroScience, 2026, PMID 42228240): "Cellular senescence can influence the tumor microenvironment, metabolic status, and immune regulation."
• Jun RORA Targeting PRNP Modulates Age-Related Cataract via Activation Oxidative Injury-Induced Cellular Senescence and Apoptosis of Lens Epithelial Cells. (Aging cell, 2026, PMID 42160747): "In vitro experiments showed that inhibiting RORA significantly alleviated cellular senescence, enhanced the anti-apoptotic capacity of LECs, and improved their resistance to oxidative stress, whereas activating RORA exerted opposite effects."
• Jun Reduced Epidermal p21 Expression Is Identified in Some Subjects on Systemic GLP-1 Receptor Agonists: A Hypothesis-Generating Pilot Study of Metabolic Modulation in Human Skin Senescence. (Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 2026, PMID 42210884): "Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert systemic metabolic and anti-inflammatory effects that may be relevant to cellular senescence, a key driver of skin aging."
• Jun Combining bioinformatics and machine learning to analyze and validate sepsis-related cell senescence genes and potential drugs. (Renal failure, 2026, PMID 42219284): "Sepsis can induce cellular senescence, thereby exacerbating tissue damage and organ dysfunction."
• May Deep Learning-Assisted Nanomechanical Evaluation of Replicative Senescence in Human Umbilical Cord Mesenchymal Stem Cells. (Langmuir : the ACS journal of surfaces and colloids, 2026, PMID 42127096): "These findings show a new "senescence-associated mechanical phenotype" unique to hUC-MSCs."