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Briefings in Bioinformatics Jul 2019Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely... (Review)
Review
Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.
Topics: Computational Biology; Gene Regulatory Networks; Humans; Kruppel-Like Factor 4; Male; MicroRNAs; Models, Genetic; Neoplasms, Germ Cell and Embryonal; RNA, Messenger; Seminoma; Telomere Homeostasis; Telomere Shortening; Testicular Neoplasms; Transcriptome
PubMed: 29579225
DOI: 10.1093/bib/bby020 -
Cells Jan 2019Telomeres with G-rich repetitive DNA and particular proteins as special heterochromatin structures at the termini of eukaryotic chromosomes are tightly maintained to... (Review)
Review
Telomeres with G-rich repetitive DNA and particular proteins as special heterochromatin structures at the termini of eukaryotic chromosomes are tightly maintained to safeguard genetic integrity and functionality. Telomerase as a specialized reverse transcriptase uses its intrinsic RNA template to lengthen telomeric G-rich strand in yeast and human cells. Cells sense telomere length shortening and respond with cell cycle arrest at a certain size of telomeres referring to the "Hayflick limit." In addition to regulating the cell replicative senescence, telomere biology plays a fundamental role in regulating the chronological post-mitotic cell ageing. In this review, we summarize the current understandings of telomere regulation of cell replicative and chronological ageing in the pioneer model system and provide an overview on telomere regulation of animal lifespans. We focus on the mechanisms of survivals by telomere elongation, DNA damage response and environmental factors in the absence of telomerase maintenance of telomeres in the yeast and mammals.
Topics: Animals; Cellular Senescence; DNA Repair; Humans; Longevity; Mice; Models, Biological; Saccharomyces cerevisiae; Telomere; Telomere Homeostasis; Telomere Shortening
PubMed: 30650660
DOI: 10.3390/cells8010054 -
Advances in Nutrition (Bethesda, Md.) Nov 2020Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered... (Meta-Analysis)
Meta-Analysis
Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered to be 1 of the most recognized diets for disease prevention and healthy aging, partially due to its demonstrated anti-inflammatory and antioxidative properties which may impact on telomere length (TL). The aim of this meta-analysis was to determine the associations between MedDiet adherence and TL maintenance. MEDLINE-PubMed and Cochrane databases were searched up to December 2018 for studies evaluating the association between MedDiet adherence and TL in blood cells. Two reviewers, working independently, screened all titles and abstracts to identify studies that met the inclusion criteria [cross-sectional, case-control, and prospective cohort studies and randomized clinical trials (RCTs) published in English and excluded nonoriginal articles]. Data were pooled by the generic inverse variance method using the random effects model and expressed as standardized mean difference (SMD). Heterogeneity was identified using the Cochran Q test and quantified by the I2 statistic. A total of 8 original cross-sectional studies were included for the quantitative meta-analysis, comprising a total of 13,733 participants from 5 countries. A positive association between adherence to the MedDiet and TL was observed in all meta-analyses, with the exception of those conducted only in men: SMD (95% CI) of 0.130 (0.029; 0.231) for all subjects, 0.078 (0.005; 0.152) for women, and 0.095 (-0.005; 0.195) for men. Only 1 prospective cohort study and 1 RCT were identified, therefore, we could not undertake a meta-analysis for these study designs. The present meta-analysis of cross-sectional studies demonstrates that higher MedDiet adherence is associated with longer TL. At the same time, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.
Topics: Cross-Sectional Studies; Diet, Mediterranean; Humans; Prospective Studies; Telomere; Telomere Shortening
PubMed: 32730558
DOI: 10.1093/advances/nmaa079 -
International Journal of Molecular... Nov 2021Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis.... (Review)
Review
Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis. Histologically, aging skin typically shows epidermal atrophy due to decreased cell numbers. The dermis of aged skin shows decreased numbers of mast cells and fibroblasts. Fibroblast senescence contributes to skin aging by secreting a senescence-associated secretory phenotype, which decreases proliferation by impairing the release of essential growth factors and enhancing degradation of the extracellular matrix through activation of matrix metalloproteinases (MMPs). Several molecular mechanisms affect skin aging including telomere shortening, oxidative stress and MMP, cytokines, autophagic control, microRNAs, and the microbiome. Accumulating evidence on the molecular mechanisms of skin aging has provided clinicians with a wide range of therapeutic targets for treating aging skin.
Topics: Atrophy; Cell Proliferation; Cellular Senescence; Epidermal Cells; Fibroblasts; Humans; Mast Cells; Matrix Metalloproteinases; Skin Aging; Telomere Shortening
PubMed: 34830368
DOI: 10.3390/ijms222212489 -
Aging Cell Apr 2021The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal... (Review)
Review
The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti-senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of "cellular aging": the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.
Topics: Aging; Animals; Biomarkers; Cell Cycle Checkpoints; Cell Division; Cell Proliferation; Cell Size; Cellular Senescence; DNA Breaks, Double-Stranded; Humans; Phenotype; Telomere Shortening
PubMed: 33711211
DOI: 10.1111/acel.13338 -
Science (New York, N.Y.) Sep 2020Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little...
Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation affects TL in multiple tissue types and that TL may mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.
Topics: Aging; Genetic Markers; Genetic Variation; Humans; Organ Specificity; Telomere; Telomere Homeostasis; Telomere Shortening
PubMed: 32913074
DOI: 10.1126/science.aaz6876 -
Journal of Applied Genetics May 2015Osteoarthritis is the most common disease of joints caused by degradation of articular cartilage and subchondral bone. It is classified as primary form with unknown... (Review)
Review
Osteoarthritis is the most common disease of joints caused by degradation of articular cartilage and subchondral bone. It is classified as primary form with unknown cause and as secondary form with known etiology. Genetic and epigenetic factors interact with environmental factors and contribute to the development of primary osteoarthritis. Thus far, many polymorphisms associated with osteoarthritis have been identified and recent studies also indicate the involvement of epigenetic factors (e.g., telomere shortening) in the initiation of this disorder. Accelerated shortening of telomeres was detected in osteoarthritis and other age-related diseases. Studies revealed that telomere length is severely reduced in blood leukocytes and chondrocytes of patients with osteoarthritis, and this may contribute to the initiation and development of osteoarthritis, whose major cause is still unknown.
Topics: Aging; Animals; Cartilage, Articular; Chondrocytes; Disease Models, Animal; Epigenesis, Genetic; Humans; Osteoarthritis; Telomere Shortening
PubMed: 25366419
DOI: 10.1007/s13353-014-0251-8 -
American Journal of Reproductive... May 2018There exists a strong correlation between unscheduled inflammation at the maternal-fetal interface and the continuum of pregnancy complications. In normal pregnancy,... (Review)
Review
There exists a strong correlation between unscheduled inflammation at the maternal-fetal interface and the continuum of pregnancy complications. In normal pregnancy, immunological tolerance is established to protect the semi-allogeneic fetus. There has been extensive research on how the immunity, endovascular trophoblast migration, and hormonal nexus are orchestrated during pregnancy at the maternal-fetal interface to program a normal pregnancy outcome. It is not clear what contributes to the plasticity of uterine immune tolerance, fetal survial, and long-term post-partum health of the mother and the offspring. Old and new concepts have reemerged and emerged that include cell-free fetal DNA (cffDNA), telomere shortening, microchimerism involving bidirectional migration of maternal and fetal cells, and pregnancy as a stress factor. The question is how these pathways converge in a gestational age-dependent manner to contribute to the health of the mother and the offspring later in life and respond to an array of inflammatory challenges. In this Review, we provide pertinent discussion on maternal-fetal cross talk through cffDNA, telomere shortening, and microchimerism in the context of inflammatory and anti-inflammatory settings, particularly how these pathways lead to normal and adverse pregnancy outcomes.
Topics: Animals; Chimerism; DNA; Female; Fetus; Humans; Inflammation; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Telomere Shortening
PubMed: 29577468
DOI: 10.1111/aji.12851 -
Cells Jan 2019Telomeres, the protective structures of chromosome ends are gradually shortened by each cell division, eventually leading to senescence or apoptosis. Cancer cells... (Review)
Review
Telomeres, the protective structures of chromosome ends are gradually shortened by each cell division, eventually leading to senescence or apoptosis. Cancer cells maintain the telomere length for unlimited growth by telomerase reactivation or a recombination-based mechanism. Recent genome-wide analyses have unveiled genetic and epigenetic alterations of the telomere maintenance machinery in cancer. While telomerase inhibition reveals that longer telomeres are more advantageous for cell survival, cancer cells often have paradoxically shorter telomeres compared with those found in the normal tissues. In this review, we summarize the latest knowledge about telomere length alterations in cancer and revisit its rationality. Finally, we discuss the potential utility of telomere length as a prognostic biomarker.
Topics: Animals; Epigenesis, Genetic; Humans; Mutation; Neoplasms; Promoter Regions, Genetic; Telomerase; Telomere Shortening
PubMed: 30709063
DOI: 10.3390/cells8020107 -
Frontiers in Immunology 2023Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer's disease (AD), Parkinson's disease... (Review)
Review
Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). Age is a major risk factor for NDs. Telomere shortening is a biological marker of cellular aging, and telomerase reverse transcriptase (TERT) has been shown to slow down this process by maintaining telomere length. The blood-brain barrier (BBB) makes the brain a unique immune organ, and while the number of T cells present in the central nervous system is limited, they play an important role in NDs. Research suggests that NDs can be influenced by modulating peripheral T cell immune responses, and that TERT may play a significant role in T cell senescence and NDs. This review focuses on the current state of research on TERT in NDs and explores the potential connections between TERT, T cells, and NDs. Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases.
Topics: Humans; Cellular Senescence; Neurodegenerative Diseases; Telomerase; Telomere Shortening; T-Lymphocytes
PubMed: 37063844
DOI: 10.3389/fimmu.2023.1165632