Aging is a biological process characterized by a progressive functional decline in tissues and organs, which eventually leads to mortality. Telomeres, the repetitive DNA repeat sequences at the end of linear eukaryotic chromosomes protecting chromosome ends from degradation and illegitimate recombination, play a crucial role in cell fate and aging. Due to the mechanism of replication, telomeres shorten as cells proliferate, which consequently contributes to cellular senescence and mitochondrial dysfunction. Cells are the basic unit of organismal structure and function, and mitochondria are the powerhouse and metabolic center of cells. Therefore, cellular senescence and mitochondrial dysfunction would result in tissue or organ degeneration and dysfunction followed by somatic aging through multiple pathways. In this review, we summarized the main mechanisms of cellular senescence, mitochondrial malfunction and aging triggered by telomere attrition. Understanding the molecular mechanisms involved in the aging process may elicit new strategies for improving health and extending lifespan.

Background. Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis. Telomeric repeat-binding factor 2 (TRF2) is a critical telomere protection protein. Emerging evidence indicates that TRF2 may be an essential treatment option for GC; however, the exact mechanism remains largely unknown. Objective. We aimed to explore the role of TRF2 in GC cells. The function and molecular mechanisms of TRF2 in the pathogenesis of GC were mainly discussed in this study. Methods. Relevant data from GEPIA and TCGA databases regarding TRF2 gene expression and its prognostic significance in GC samples were analyzed. Analysis of 53BP1 foci at telomeres by immunofluorescence, metaphase spreads, and telomere-specific FISH analysis was carried out to explore telomere damage and dysfunction after TRF2 depletion. CCK8 cell proliferation, trypan blue staining, and colony formation assay were performed to evaluate cell survival. Apoptosis and cell migration were determined with flow cytometry and scratch-wound healing assay, respectively. qRT-PCR and Western blotting were carried out to analyze the mRNA and protein expression levels after TRF2 depletion on apoptosis, autophagic death, and ferroptosis. Results. By searching with GEPIA and TCGA databases, the results showed that the expression levels of TRF2 were obviously elevated in the samples of GC patients, which was associated with adverse prognosis. Knockdown of TRF2 suppressed the cell growth, proliferation, and migration in GC cells, causing significant telomere dysfunction. Apoptosis, autophagic death, and ferroptosis were also triggered in this process. The pretreatment of chloroquine (autophagy inhibitor) and ferrostatin-1 (ferroptosis inhibitor) improved the survival phenotypes of GC cells. Conclusion. Our data suggest that TRF2 depletion can inhibit cell growth, proliferation, and migration through the combined action of ferroptosis, autophagic death, and apoptosis in GC cells. The results indicate that TRF2 might be used as a potential target to develop therapeutic strategies for treating GC.

Background Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.

Background: Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results: In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions: Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.