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Telomere research

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https://www.readbyqxmd.com/read/29335381/the-fetal-programming-of-telomere-biology-hypothesis-an-update
#1
REVIEW
Sonja Entringer, Karin de Punder, Claudia Buss, Pathik D Wadhwa
Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29335375/reflections-on-telomere-dynamics-and-ageing-related-diseases-in-humans
#2
REVIEW
Abraham Aviv, Jerry W Shay
Epidemiological studies have principally relied on measurements of telomere length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL (LTL) displays vast variation across individuals-a phenomenon already observed in newborns. It is highly heritable, longer in females than males and in individuals of African ancestry than European ancestry. LTL is also longer in offspring conceived by older men. The traditional view regards LTL as a passive biomarker of human ageing. However, new evidence suggests that a dynamic interplay between selective evolutionary forces and TL might result in trade-offs for specific health outcomes...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29335371/the-relationship-between-telomere-length-and-mortality-risk-in-non-model-vertebrate-systems-a-meta-analysis
#3
Rachael V Wilbourn, Joshua P Moatt, Hannah Froy, Craig A Walling, Daniel H Nussey, Jelle J Boonekamp
Telomere length (TL) has become a biomarker of increasing interest within ecology and evolutionary biology, and has been found to predict subsequent survival in some recent avian studies but not others. Here, we undertake the first formal meta-analysis to test whether there is an overall association between TL and subsequent mortality risk in vertebrates other than humans and model laboratory rodents. We identified 27 suitable studies and obtained standardized estimates of the hazard ratio associated with TL from each...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29335364/experimental-manipulation-of-telomere-length-does-it-reveal-a-corner-stone-role-for-telomerase-in-the-natural-variability-of-individual-fitness
#4
REVIEW
F Criscuolo, S Smith, S Zahn, B J Heidinger, M F Haussmann
Telomeres, the non-coding ends of linear chromosomes, are thought to be an important mechanism of individual variability in performance. Research suggests that longer telomeres are indicative of better health and increased fitness; however, many of these data are correlational and whether these effects are causal are poorly understood. Experimental tests are emerging in medical and laboratory-based studies, but these types of experiments are rare in natural populations, which precludes conclusions at an evolutionary level...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29321523/integrative-genomic-and-transcriptomic-analysis-of-leiomyosarcoma
#5
Priya Chudasama, Sadaf S Mughal, Mathijs A Sanders, Daniel Hübschmann, Inn Chung, Katharina I Deeg, Siao-Han Wong, Sophie Rabe, Mario Hlevnjak, Marc Zapatka, Aurélie Ernst, Kortine Kleinheinz, Matthias Schlesner, Lina Sieverling, Barbara Klink, Evelin Schröck, Remco M Hoogenboezem, Bernd Kasper, Christoph E Heilig, Gerlinde Egerer, Stephan Wolf, Christof von Kalle, Roland Eils, Albrecht Stenzinger, Wilko Weichert, Hanno Glimm, Stefan Gröschel, Hans-Georg Kopp, Georg Omlor, Burkhard Lehner, Sebastian Bauer, Simon Schimmack, Alexis Ulrich, Gunhild Mechtersheimer, Karsten Rippe, Benedikt Brors, Barbara Hutter, Marcus Renner, Peter Hohenberger, Claudia Scholl, Stefan Fröhling
Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. Here we show, using whole-exome and transcriptome sequencing, that LMS tumors are characterized by substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations including chromothripsis, and frequent whole-genome duplication. Furthermore, we detect alternative telomere lengthening in 78% of cases and identify recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and SP100, providing insight into the genetic basis of this mechanism...
January 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29321190/genomic-landscape-of-pancreatic-neuroendocrine-tumours-the-international-cancer-genome-consortium
#6
Andrea Mafficini, Aldo Scarpa
Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes, and hyperactivation of the PI3K/mTOR pathway...
January 10, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29288666/zeb1-stimulates-breast-cancer-growth-by-up-regulating-htert-expression
#7
Pan Yu, Xi Shen, Wen Yang, Yunke Zhang, Chunping Liu, Tao Huang
Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29274177/links-between-parental-life-histories-of-wild-salmon-and-the-telomere-lengths-of-their-offspring
#8
D McLennan, J D Armstrong, D C Stewart, S Mckelvey, W Boner, P Monaghan, N B Metcalfe
The importance of parental contributions to offspring development and subsequent performance is self-evident at a genomic level; however, parents can also affect offspring fitness by indirect genetic and environmental routes. The life history strategy that an individual adopts will be influenced by both genes and environment; and this may have important consequences for offspring. Recent research has linked telomere dynamics (i.e. telomere length and loss) in early life to future viability and longevity. Moreover, a number of studies have reported a heritable component to telomere length across a range of vertebrates, though the effects of other parental contribution pathways have been far less studied...
December 23, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29260452/emerging-roles-of-sirtuin-6-in-alzheimer-s-disease
#9
REVIEW
Nurul Fatihah Mohamad Nasir, Azalina Zainuddin, Shaharum Shamsuddin
Alzheimer's disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded...
December 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29244163/regulation-of-chromosome-segregation-in-oocytes-and-the-cellular-basis-for-female-meiotic-errors
#10
Jessica Greaney, Zhe Wei, Hayden Homer
BACKGROUND: Meiotic chromosome segregation in human oocytes is notoriously error-prone, especially with ageing. Such errors markedly reduce the reproductive chances of increasing numbers of women embarking on pregnancy later in life. However, understanding the basis for these errors is hampered by limited access to human oocytes. OBJECTIVE AND RATIONALE: Important new discoveries have arisen from molecular analyses of human female recombination and aneuploidy along with high-resolution analyses of human oocyte maturation and mouse models...
December 13, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29233913/reference-quality-genome-assemblies-of-three-parastagonospora-nodorum%C3%A2-isolates-differing-in-virulence-on-wheat
#11
Jonathan K Richards, Nathan A Wyatt, Zhaohui Liu, Justin D Faris, Timothy L Friesen
Parastagonospora nodorum, the causal agent of Septoria nodorum blotch of wheat, has emerged as a model necrotrophic fungal organism for the study of host-microbe interactions. To date, three necrotrophic effectors have been identified and characterized from this pathogen, including SnToxA, SnTox1, and SnTox3. Necrotrophic effector identification was greatly aided by the development of a draft genome of Australian isolate SN15 via Sanger sequencing, yet remained largely fragmented. This research presents the development of near-finished genomes of P...
December 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29213278/translating-measures-of-biological-aging-to-test-effectiveness-of-geroprotective-interventions-what-can-we-learn-from-research-on-telomeres
#12
Waylon J Hastings, Idan Shalev, Daniel W Belsky
Intervention studies in animals suggest molecular changes underlying age-related disease and disability can be slowed or reversed. To speed translation of these so-called "geroprotective" therapies to prevent age-related disease and disability in humans, biomarkers are needed that can track changes in the rate of human aging over the course of intervention trials. Algorithm methods that measure biological processes of aging from combinations of DNA methylation marks or clinical biomarkers show promise. To identify next steps for establishing utility of these algorithm-based measures of biological aging for geroprotector trials, we considered the history a candidate biomarker of aging that has received substantial research attention, telomere length...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29207465/%C3%AE-pna-fret-pair-miniprobes-for-quantitative-fluorescent-in-situ-hybridization-to-telomeric-dna-in-cells-and-tissue
#13
Alexander Orenstein, April S Berlyoung, Elizabeth E Rastede, Ha H Pham, Elise Fouquerel, Connor T Murphy, Brian J Leibowitz, Jian Yu, Tumul Srivastava, Bruce A Armitage, Patricia L Opresko
Measurement of telomere length by fluorescent in situ hybridization is widely used for biomedical and epidemiological research, but there has been relatively little development of the technology in the 20 years since it was first reported. This report describes the use of dual gammaPNA (γPNA) probes that hybridize at alternating sites along a telomere and give rise to Förster resonance energy transfer (FRET) signals. Bright staining of telomeres is observed in nuclei, chromosome spreads and tissue samples...
December 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29204651/whole-exome-sequencing-in-adults-with-chronic-kidney-disease-a-pilot-study
#14
Sneh Lata, Maddalena Marasa, Yifu Li, David A Fasel, Emily Groopman, Vaidehi Jobanputra, Hila Rasouly, Adele Mitrotti, Rik Westland, Miguel Verbitsky, Jordan Nestor, Lindsey M Slater, Vivette D'Agati, Marcin Zaniew, Anna Materna-Kiryluk, Francesca Lugani, Gianluca Caridi, Luca Rampoldi, Aditya Mattoo, Chad A Newton, Maya K Rao, Jai Radhakrishnan, Wooin Ahn, Pietro A Canetta, Andrew S Bomback, Gerald B Appel, Corinne Antignac, Glen S Markowitz, Christine K Garcia, Krzysztof Kiryluk, Simone Sanna-Cherchi, Ali G Gharavi
Background: The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. Objective: To study the diagnostic utility of WES in a selected referral population of adults with CKD. Design: Observational cohort. Setting: A major academic medical center...
December 5, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/29197377/regulation-of-terra-on-telomeric-and-mitochondrial-functions-in-ipf-pathogenesis
#15
Yulin Gao, Jinjin Zhang, Yuxia Liu, Songzi Zhang, Youlei Wang, Bo Liu, Huizhu Liu, Rongrong Li, Changjun Lv, Xiaodong Song
BACKGROUND: Aging is a known risk factor of idiopathic pulmonary fibrosis (IPF). However, the pathogenic mechanisms underlying the effects of advanced aging remain largely unknown. Telomeric repeat-containing RNA (TERRA) represents a type of long noncoding RNA. In this study, the regulatory roles of TERRA on human telomeres and mitochondria and IPF epithelial injury model were identified. METHODS: Blood samples were collected from patients with IPF (n = 24) and matched control individuals (n = 24)...
December 2, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29192673/trfh-domain-at-the-root-of-telomere-protein-evolution
#16
Marie-Joseph Giraud-Panis, Jing Ye, Eric Gilson
Two articles in Cell Research focus on the structure-function relationships in the shelterin complex that binds to telomeres and is essential for their stability and functions. These studies concerning both mammalian and Schizosaccharomyces pombe proteins reveal unexpected structural conservation of a motif called TRFH (Telomeric Repeat Factors Homology) domain between several subunits in these complexes, providing a rationale for further dissection of the role of telomeres in chromosome stability, aging and cancer, and encouraging us to revisit the evolution of telomere proteins...
December 1, 2017: Cell Research
https://www.readbyqxmd.com/read/29187657/-based-on-empirical-research-a-preliminary-study-on-application-of-the-social-aging-scale-for-healthy-people
#17
Ni Zeng, Pengfei Deng, Yao Long, Fei Lin, Helang Huang
To build a social aging scale for healthy people, and get the accuracy and feasibility of the scale to judge the aging of healthy people on the basis of the empirical research.
 Methods: Stratified random sampling was conducted according to the nine different age groups, and the age-related social function information was collected for healthy people by using the scale, which was made in our own plant; the distribution of the score, the correlations between the score and age or telomere length were analyzed by statistical software...
November 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29186077/telomeres-aging-and-exercise-guilty-by-association
#18
REVIEW
Warrick Chilton, Brendan O'Brien, Fadi Charchar
Telomeres are repetitive tandem DNA sequences that cap chromosomal ends protecting genomic DNA from enzymatic degradation. Telomeres progressively shorten with cellular replication and are therefore assumed to correlate with biological and chronological age. An expanding body of evidence suggests (i) a predictable inverse association between telomere length, aging and age-related diseases and (ii) a positive association between physical activity and telomere length. Both hypotheses have garnered tremendous research attention and broad consensus; however, the evidence for each proposition is inconsistent and equivocal at best...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29184185/cellular-senescence-in-gastrointestinal-diseases-from-pathogenesis-to-therapeutics
#19
REVIEW
Nina Frey, Sascha Venturelli, Lars Zender, Michael Bitzer
Senescence is a durable cell cycle arrest that can be induced in response to various stress factors, such as telomere erosion, DNA damage or the aberrant activation of oncogenes. In addition to its well-established role as a stress response programme, research has revealed important physiological roles of senescence in nondisease settings, such as embryonic development, wound healing, tissue repair and ageing. Senescent cells secrete various cytokines, chemokines, matrix remodelling proteases and growth factors, a phenotype collectively referred to as the senescence-associated secretory phenotype...
November 29, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29171222/-molecular-regulative-mechanisms-of-aging-and-interventional-effects-of-chinese-herbal-medicine
#20
REVIEW
Bu-Hui Liu, Yi-Huang Gu, Yue Tu, Wei-Ming He, Wei Wu, Ying-Lu Liu, Zi-Yue Wan, Yi-Gang Wan
Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA (mtDNA)and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide(NMN)and FOXO4-DRI,a peptide of anti-aging...
August 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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