Cellular senescence, one of the hallmarks of cancer, is characterized by cell cycle arrest and the loss of most normal cellular functions while acquiring a hypersecretory, proinflammatory phenotype. The function of senescent cells in cancer cells varies depending on the cellular conditions. Before the occurrence of cancer, senescent cells act as a barrier to prevent its development. But once cancer has occurred, senescent cells play a procancer role. However, few of the current studies have adequately explained the diversity of cellular senescence across cancers. Herein, we concluded the latest intrinsic mechanisms of cellular senescence in detail and emphasized the senescence-associated secretory phenotype as a key contributor to heterogeneity of senescent cells in tumor. We also discussed five kinds of inducers of cellular senescence and the advancement of senolytics in cancer, which are drugs that tend to clear senescent cells. Finally, we summarized the various effects of senescent cells in different cancers and manifested that their functions may be diametrically opposed under different circumstances. In short, this paper contributes to the understanding of the diversity of cellular senescence in cancers and provides novel insight for tumor therapy.

Senescence refers to a cellular state marked by irreversible cell cycle arrest and the secretion of pro-inflammatory and tissue-remodeling factors. The senescence associated secretory phenotype (SASP) impacts the tissue microenvironment and provides cues for the immune system to eliminate senescent cells (SCs). Cellular senescence has a dual nature; it can be beneficial during embryonic development, tissue repair, and tumor suppression, but it can also be detrimental in the context of chronic stress, persistent tissue injury, together with an impairment in SC clearance. Recently, the accumulation of SCs has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), a progressive condition affecting the pre-capillary pulmonary arterial bed. PAH is characterized by endothelial cell (EC) injury, inflammation, and proliferative arterial remodeling, which leads to right heart failure and premature mortality. While vasodilator therapies can improve symptoms, there are currently no approved treatments capable of reversing the obliterative arterial remodeling. Ongoing endothelial injury and dysfunction is central to the development of PAH, perpetuated by hemodynamic perturbation leading to pathological intimal shear stress. The precise role of senescent ECs in PAH remains unclear. Cellular senescence may facilitate endothelial repair, particularly in the early stages of disease. However, in more advanced disease the accumulation of senescent ECs may promote vascular inflammation and occlusive arterial remodeling. In this review, we will examine the evidence that supports a role of endothelial cell senescence to the pathogenesis of PAH. Furthermore, we will compare and discuss the apparent contradictory outcomes with the use of interventions targeting cellular senescence in the context of experimental models of pulmonary hypertension. Finally, we will attempt to propose a framework for the understanding of the complex interplay between EC injury, senescence, inflammation and arterial remodeling, which can guide further research in this area and the development of effective therapeutic strategies.

UNASSIGNED: The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.
UNASSIGNED: Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).
UNASSIGNED: The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.
UNASSIGNED: Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.

Cellular senescence represents a condition of irreversible cell cycle arrest, characterized by heightened senescence-associated beta-galactosidase (SA-β-Gal) activity, senescence-associated secretory phenotype (SASP), and activation of the DNA damage response (DDR). Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease (ESRD) globally, with ongoing unmet needs in terms of current treatments. The role of senescence in the pathogenesis of DKD has attracted substantial attention with evidence of premature senescence in this condition. The process of cellular senescence in DKD appears to be associated with mitochondrial redox pathways, autophagy, and endoplasmic reticulum (ER) stress. Increasing accumulation of senescent cells in the diabetic kidney not only leads to an impaired capacity for repair of renal injury, but also the secretion of pro-inflammatory and profibrotic cytokines and growth factors causing inflammation and fibrosis. Current treatments for diabetes exhibit varying degrees of renoprotection, potentially via mitigation of senescence in the diabetic kidney. Targeting senescent cell clearance through pharmaceutical interventions could emerge as a promising strategy for preventing and treating DKD. In this paper, we review the current understanding of senescence in DKD and summarize the possible therapeutic interventions relevant to senescence in this field.

Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying the determinants of the duration of immunity. The quality and persistence of circulating CD4 effector memory (TEM) and central memory (TCM) T cells in mice appear to shift with age, but it is unclear whether these changes are driven by the aging host environment, by cell age effects, or both. Here, we address these issues by combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, and mathematical models. Together, these allow us to quantify the dynamics of both young and established circulating memory CD4 T cell subsets, within both young and old mice. We show that that these cells and their descendents become more persistent the longer they reside within the TCM and TEM pools. This behaviour may limit memory CD4 T cell diversity by skewing TCR repertoires towards clones generated early in life, but may also compensate for functional defects in new memory cells generated in old age.

UNASSIGNED: This study aims to identify differentially expressed genes (DEGs) between high-risk and non-high-risk groups in neuroblastoma (NB), construct a prognostic model, and establish a risk score formula.
UNASSIGNED: The NB dataset GSE49710 (n = 498) from the GEO database served as the training cohort to select DEGs between high-risk and non-high-risk NB groups. Cellular senescence-related genes were obtained from the Aging Atlas database. Intersection genes from both datasets were identified as key genes of cellular senescence-related genes (SRGs). A prognostic model was constructed using Univariate Cox regression analysis and the Lasso algorithm with SRGs. Validation was performed using the E-MTAB-8248 cohort (n = 223). The expression levels of AURKA and CENPA were evaluated via RT-qPCR in two clinical NB sample groups.
UNASSIGNED: Eight SRGs were identified, and a prognostic model comprising five genes related to cellular senescence was constructed. AURKA and CENPA showed significant expression in clinical samples and were closely associated with cellular senescence.
UNASSIGNED: The prognostic model consisted with five cellular senescence related genes effectively predicts the prognosis of NB patients. AURKA and CENPA represent promising targets in NB for predicting cellular senescence, offering potential insights for NB therapy.

HMGA1 is an abundant non-histone chromatin protein that has been implicated in embryonic development, cancer, and cellular senescence, but its specific role remains elusive. Here, we combine functional genomics approaches with graph theory to investigate how HMGA1 genomic deposition controls high-order chromatin networks in an oncogene-induced senescence model. While the direct role of HMGA1 in gene activation has been described previously, we find little evidence to support this. Instead, we show that the heterogeneous linear distribution of HMGA1 drives a specific 3D chromatin organization. HMGA1-dense loci form highly interactive networks, similar to, but independent of, constitutive heterochromatic loci. This, coupled with the exclusion of HMGA1-poor chromatin regions, leads to coordinated gene regulation through the repositioning of genes. In the absence of HMGA1, the whole process is largely reversed, but many regulatory interactions also emerge, amplifying the inflammatory senescence-associated secretory phenotype. Such HMGA1-mediated fine-tuning of gene expression contributes to the heterogeneous nature of senescence at the single-cell level. A similar \'buffer\' effect of HMGA1 on inflammatory signalling is also detected in lung cancer cells. Our study reveals a mechanism through which HMGA1 modulates chromatin compartmentalization and gene regulation in senescence and beyond.

UNASSIGNED: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC.
UNASSIGNED: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism.
UNASSIGNED: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset.
UNASSIGNED: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.

Understanding the complex dynamics of telomere biology is important in the strong link between aging and cancer. Telomeres, the protective caps at the end of chromosomes, are central players in this connection. While their gradual shortening due to replication limits tumors expansion by triggering DNA repair mechanisms, it also promotes oncogenic changes within chromosomes, thus sustaining tumorigenesis. The enzyme telomerase, responsible for maintaining telomere length, emerges as a central player in this context. Its expression in cancer cells facilitates the preservation of telomeres, allowing them to circumvent the growth-limiting effects of short telomeres. Interestingly, the influence of telomerase extends beyond telomere maintenance, as evidenced by its involvement in promoting cell growth through alternative pathways. In this context, inflammation accelerates telomere shortening, resulting in telomere dysfunction, while telomere elements also play a role in modulating the inflammatory response. The recognition of this interplay has promoted the development of novel therapeutic approaches centered around telomerase inhibition. This review provides a comprehensive overview of the field, emphasizing recent progress in knowledge and the implications in understanding of cancer biology.

The senescence of bone marrow mesenchymal stromal cells (MSCs) leads to the impairment of stemness and osteogenic differentiation capacity. In a previous study, we screened out stearoyl-CoA desaturase 2 (SCD2), the most evidently changed differential gene in lipid metabolism, using combined transcriptomic and metabolomic analyses, and verified that SCD2 could mitigate MSC senescence. However, the underlying molecular mechanism by which the rate-limiting enzyme of lipogenesis SCD2 manipulates MSC senescence has not been completely understood. In this study, we demonstrate that SCD2 over-expression alleviates MSC replicative senescence and ameliorates their osteogenic differentiation through the regulation of lipogenesis. Furthermore, SCD2 expression is reduced, whereas miR-200c-3p expression is elevated in replicative senescent MSCs. SCD2 is the direct target gene of miR-200c-3p, which can bind to the 3\'-UTR of SCD2. MiR-200c-3p replenishment in young MSCs is able to diminish SCD2 expression levels due to epigenetic modulation. In addition, SCD2-rescued MSC senescence and enhanced osteogenic differentiation can be attenuated by miR-200c-3p repletion via suppressing lipogenesis. Taken together, we reveal the potential mechanism of SCD2 influencing MSC senescence from the perspective of lipid metabolism and epigenetics, which provides both an experimental basis for elucidating the mechanism of stem cell senescence and a novel target for delaying stem cell senescence.