As an important telomere binding protein, TPP1 protects the ends of telomeres and maintains the stability and integrity of its structure and function by interacting with other five essential core proteins (POT1, TRF1, TRF2, TIN2, and RAP1) to form a complex called Shelterin. Recently, researchers have discovered that TPP1 participates in protection of telomeres and regulation of telomerase activity. The relationship between TPP1 and tumorigenesis, tumor progression and treatment has also been investigated. This paper reviews the latest findings of TPP1 regarding to its structure, function and interaction with other proteins involved in tumorigenesis.
Chromosomal Instability ; DNA Damage ; Humans ; Neoplasms ; genetics ; Telomere ; Telomere-Binding Proteins ; chemistry ; physiology

Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere-elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.
Animals ; Mice ; Mice, Knockout ; Telomerase/genetics/*metabolism ; Telomere/metabolism

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

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

Potential maximum life span of humans is estimated around 115-120 years by Cutler. His estimate agrees with an earlier observation by Buffon who claimed that animals tended to live six times the period needed to complete their growth. As humans reach their skeletal maturity at approximately 20 years. Life span has not changed throughout recorded history. Life expectany, the actual average survival for certain given population has increased thanks to social, economic and medical advances. There are two basic levels of biological explanations on aging: macrobiological and microbiological. Macrobiological explanation includes homeostasis, immune system, endocrine, lifestyle, nutrition and environment. Microbiological explanation includes cellular clock theory, free radical theory and metabolic theory with nutrition and antioxidants. Recent advances of genetics opened new era on telomere and telemorase. Gene therapy is applied mainly at the laboratory or limited as local use under investigation. Although the results are encouraging at the laboratory, application for clinical purpose will need tremendous thorough trial and errors.
Aging ; Animals ; Antioxidants ; Genetic Therapy ; Genetics ; Homeostasis ; Humans ; Immune System ; Life Style ; Telomere

To explore the relationship between telomere length changes and age, and to provide data and reference for further study of geriatric medical problems.
 Methods: The healthy people over 20 years old were chosen as subject from several hospitals by random sampling method, and their peripheral blood samples were collected. The relative length of telomere was detected by quantitative real-time PCR, and the relationship between age and telomere length was analyzed by statistical software.
 Results: A total of 1 022 samples were obtained. There were significant differences in the relative telomere length among different age groups (F=21.492, P<0.001). Telomere length and age showed negative correlation (r=-0.325, P<0.001), the regression equation was y=-0.008x+1.772 (x for age, y for the average telomere length, P<0.001).
 Conclusion: The telomere length for peripheral blood leukocytes in healthy people varies between different age groups, suggesting that telomere length gradually decreases with age.
Adult ; Age Factors ; Humans ; Leukocytes, Mononuclear ; Regression Analysis ; Telomere ; genetics ; Young Adult

Cholinesterases/genetics* ; Dimethoate/analogs & derivatives* ; Humans ; Occupational Exposure/adverse effects* ; Polymorphism, Genetic ; Telomere

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

Child ; Chromosome Aberrations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Male ; Telomere

Carcinoma, Squamous Cell ; genetics ; Cell Division ; Chromosome Deletion ; Humans ; Laryngeal Neoplasms ; genetics ; Telomere ; genetics ; Tumor Cells, Cultured