BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

OBJECTIVE: To summarize the clinical characteristics, diagnosis, treatment and prognosis of dyskeratosis congenita (DC) in children, and to provide clinical experience for the diagnosis and treatment of DC. METHODS: The clinical data of children with dyskeratosis congenital admitted to Children's Hospital of Soochow University from May 2016 to May 2024 were retrospectively analyzed. Whole exome sequencing (WES) was performed, the patients were followed up and the related literature was reviewed. RESULTS: A total of 4 patients were enrolled. There were 1 male and 3 females. Two patients had spontaneous TINF2 mutation, one had TERT mutation, and one had DKC1 mutation. All of them had bone marrow hypoplasia. Two patients underwent allogeneic hematopoietic stem cell transplantation, and both had good engraftment. Anti-rejection drugs were stopped, and they survived more than 5 years of follow-up. One patient was followed up in outpatient department, and another patient was scheduled to undergo hematopoietic stem cell transplantation. CONCLUSION The onset of dyskeratosis congenita in children is insidious, so genetic diagnosis is particularly important. c.853_861delGTCATGCTG (p.285-287del) was a new mutation site of TINF2, which expanded the gene mutation spectrum of DC. Hematopoietic stem cell transplantation is an effective treatment for bone marrow failure, and the treatment of other organ complications depends on further genetic exploration.
Humans ; Dyskeratosis Congenita/therapy* ; Hematopoietic Stem Cell Transplantation ; Male ; Mutation ; Female ; Retrospective Studies ; Telomerase/genetics* ; Telomere-Binding Proteins/genetics* ; Child ; Cell Cycle Proteins/genetics* ; Nuclear Proteins/genetics* ; Child, Preschool ; Prognosis ; Exome Sequencing

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Previous studies mainly used β-amyloid and α-synuclein as the biomarkers for the diagnosis of neurodegenerative diseases. In recent years，studies have shown that telomeres at the end of chromosome can be used as an index to measure the degree of biological aging，and telomere length and telomerase activity may also be used as the blood markers to evaluate the risk，progression，and poor prognosis of neurodegenerative diseases in the elderly；however，there is still a lack of consistency between the research findings in China and globally. Understanding the role of telomere-related biomarkers in age-related diseases can help clinicians learn more about the mechanism of disease development and progression. This article reviews the latest research advances in the telomere-telomerase system in neurodegenerative diseases，in order to introduce the influence of telomere length and telomerase activity on neurodegenerative diseases and their potential mechanisms of action.
Telomere ; Telomerase ; Neurodegenerative Diseases ; Alzheimer Disease ; Parkinson Disease

Cellular senescence, an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile, plays a dual role in liver health and disease. Under physiological conditions, senescence aids organ repair and regeneration, but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases, including alcoholic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Senescence is identified by a range of cellular and molecular changes, such as morphological alterations, expression of cell cycle inhibitors, senescence-associated β-galactosidase activity, and nuclear membrane changes. The onset of senescence in organ cells can affect the entire organism, primarily through the senescence-associated secretory phenotype, which has autocrine, paracrine, and endocrine effects on tissue microenvironments. The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases, particularly through mechanisms like telomere shortening, genomic and mitochondrial DNA damage, and inflammation. Additionally, this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression. The therapeutic potential of these interventions, alongside their safety and effectiveness, highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.
Humans ; Cellular Senescence/physiology* ; Liver Diseases ; Animals ; DNA Damage ; Telomere Shortening/physiology*

Humans ; Neuroendocrine Tumors/genetics* ; Prognosis ; X-linked Nuclear Protein/genetics* ; Pancreatic Neoplasms/pathology* ; Telomere/pathology*

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q₁,Q₃)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q₁,Q₃)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.
Humans ; Female ; Pregnancy ; Young Adult ; Adult ; DNA Adducts ; Abortion, Missed/chemically induced* ; Polycyclic Aromatic Hydrocarbons ; Abortion, Spontaneous/chemically induced* ; Telomere/chemistry*

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Lamin B1 (LMNB1) is highly expressed in liver cancer tissues, and its influence and mechanism on the proliferation of hepatocellular carcinoma cells were explored by knocking down the expression of the protein. In liver cancer cells, siRNAs were used to knock down LMNB1. Knockdown effects were detected by Western blotting. Changes in telomerase activity were detected by telomeric repeat amplification protocol assay (TRAP) experiments. Telomere length changes were detected by quantitative real-time polymerase chain reaction (qPCR). CCK8, cloning formation, transwell and wound healing were performed to detect changes in its growth, invasion and migration capabilities. The lentiviral system was used to construct HepG2 cells that steadily knocked down LMNB1. Then the changes of telomere length and telomerase activity were detected, and the cell aging status was detected by SA-β-gal senescence staining. The effects of tumorigenesis were detected by nude mouse subcutaneous tumorigenesis experiments, subsequent histification staining of tumors, SA-β-gal senescence staining, fluorescence in situ hybridization (FISH) for telomere analysis and other experiments. Finally, the method of biogenesis analysis was used to find the expression of LMNB1 in clinical liver cancer tissues, and its relationship with clinical stages and patient survival. Knockdown of LMNB1 in HepG2 and Hep3B cells significantly reduced telomerase activity, cell proliferation, migration and invasion abilities. Experiments in cells and tumor formation in nude mice had demonstrated that stable knockdown of LMNB1 reduced telomerase activity, shortened telomere length, senesced cells, reduced cell tumorigenicity and KI-67 expression. Bioinformatics analysis showed that LMNB1 was highly expressed in liver cancer tissues and correlated with tumor stage and patient survival. In conclusion, LMNB1 is overexpressed in liver cancer cells, and it is expected to become an indicator for evaluating the clinical prognosis of liver cancer patients and a target for precise treatment.
Animals ; Mice ; Telomerase/metabolism* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Telomere Shortening ; In Situ Hybridization, Fluorescence ; Mice, Nude ; Telomere/pathology* ; Carcinogenesis

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.
Aging/pathology* ; Cellular Senescence ; Humans ; Lung/pathology* ; Lung Diseases/pathology* ; Respiration Disorders/pathology* ; Telomere ; Telomere Shortening