Cellular senescence is identified by a living cell in irreversible and persistent cell cycle arrest in response to various cellular stresses. Senescent cells secrete senescence-associated secretory phenotype factors that can amplify cellular senescence and alter the microenvironments. Radiotherapy, via ionizing radiation, serves as an effective treatment for local tumor control with side effects on normal cells, which can induce inflammation and fibrosis in irradiated and nearby regions. Research has revealed that senescent phenotype is observable in irradiated organs. This process starts with DNA damage mediated by radiation, after which a G2 arrest occurs in virtually all eukaryotic cells and a mitotic bypass is possibly necessary to ultimately establish cellular senescence. Within this complex DNA damage response signaling network, ataxia telangiectasia-mutated protein, p53, and p21 stand out as the crucial mediators. Senolytic agents, a class of small molecules that can selectively kill senescent cells, hold great potential to substantially reduce the side effects caused by radiotherapy while reasonably steer clear of carcinogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972185 | PMC |
| http://dx.doi.org/10.3389/fphar.2018.00522 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Age-dependent decline in sperm quality and function in a naturally short-lived vertebrate.
BMC Ecol Evol
January 2025
Leibniz Institute on Aging, Jena, Germany.
Maximizing the life-long reproductive output would lead to the prediction that short-lived and fast aging species would undergo no - if any - reproductive senescence. Turquoise killifish (Nothobranchius furzeri) are naturally short-lived teleosts, and undergo extensive somatic aging, characterized by molecular, cellular, and organ dysfunction following the onset of sexual maturation. Here, we tested whether naturally short-lived and fast aging male turquoise killifish maximize reproduction and display minimal - if any, reproductive senescence.
View Article and Find Full Text PDFApoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies.
Cell Death Differ
January 2025
Dana Farber Cancer Institute, Boston, MA, USA.
Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.
View Article and Find Full Text PDFLipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors.
J Immunother Cancer
January 2025
Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People's Republic of China
Background: Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.
Methods: In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase Aα (cPLAα), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.
Functional Diversity of Senescent Cells in Driving Aging Phenotypes and Facilitating Tissue Regeneration.
J Biochem
January 2025
Division of Cancer and Senescence Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the aging process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development, and repair.
View Article and Find Full Text PDFCellular Senescence in The Cancer Microenvironment.
J Biochem
January 2025
Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
In this aging society, the number of patients suffering from age-related diseases, including cancer, is increasing. Cellular senescence is a cell fate that involves permanent cell cycle arrest. Accumulated senescent cells in tissues over time present senescence-associated secretory phenotype (SASP) and make the inflammatory context, disturbing the tumor microenvironment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!