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https://www.readbyqxmd.com/read/28932625/vascular-aging-implications-for-cardiovascular-disease-and-therapy
#1
Yohannes T Ghebre, Eduard Yakubov, Wing Tak Wong, Prasanna Krishnamurthy, Nazish Sayed, Andrew G Sikora, Mark D Bonnen
The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function...
December 2016: Translational Medicine: Current Research
https://www.readbyqxmd.com/read/28930701/leukocyte-telomere-length-t-cell-composition-and-dna-methylation-age
#2
Brian H Chen, Cara L Carty, Masayuki Kimura, Jeremy D Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P Reiner, Abraham Aviv
Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826)...
September 20, 2017: Aging
https://www.readbyqxmd.com/read/28927537/interstitial-telomeric-sequences-in-vertebrate-chromosomes-origin-function-instability-and-evolution
#3
REVIEW
Alejandro D Bolzán
By definition, telomeric sequences are located at the very ends or terminal regions of chromosomes. However, several vertebrate species show blocks of (TTAGGG)n repeats present in non-terminal regions of chromosomes, the so-called interstitial telomeric sequences (ITSs), interstitial telomeric repeats or interstitial telomeric bands, which include those intrachromosomal telomeric-like repeats located near (pericentromeric ITSs) or within the centromere (centromeric ITSs) and those telomeric repeats located between the centromere and the telomere (i...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28925409/metabolic-and-genomic-adaptations-to-winter-fattening-in-a-primate-species-the-grey-mouse-lemur-microcebus-murinus
#4
J Terrien, M Gaudubois, D Champeval, V Zaninotto, L Roger, J F Riou, F Aujard
AIM: To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation. METHODS: Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur (Microcebus murinus) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages...
August 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28919432/chronic-pain-and-telomere-length-in-community-dwelling-adults-findings-from-the-1999-2002-national-health-and-nutrition-examination-survey
#5
Alta M Steward, Julia D Morgan, Juan P Espinosa, Dennis C Turk, Kushang V Patel
Chronic pain is a common condition associated with psychological distress, functional impairments, and age-associated comorbidity. Preliminary studies, based on relatively small sample sizes, suggest that the combination of chronic pain and stress is associated with telomere shortening, a widely recognized marker of cellular aging. We sought to determine the cross-sectional association of chronic pain with telomere length in 7,816 community-dwelling adults ages 20 and older who participated in the 1999-2002 National Health and Nutrition Examination Survey...
September 12, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28910708/telomere-quantification-in-frontal-and-temporal-brain-tissue-of-patients-with-schizophrenia
#6
Hans C van Mierlo, Catharina G K Wichers, Yujie He, Marjolein A M Sneeboer, Timothy R D J Radstake, René S Kahn, Jasper C A Broen, Lot D de Witte
Recent imaging studies have suggested that accelerated aging occurs in schizophrenia. However, the exact cause of these findings is still unclear. In this study we measured telomere length, a marker for cell senescence, in gray and white matter brain tissue from the medial frontal gyrus (MFG) and superior temporal gyrus (STG) of 9 patients with schizophrenia and 11 controls. No alterations in telomere length were found in MFG gray and white matter and in STG gray matter. A significant reduction in telomere length was observed in STG white matter of patients with schizophrenia as compared to controls (fold change of -0...
September 7, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28904242/the-g-quadruplex-dna-stabilizing-drug-pyridostatin-promotes-dna-damage-and-downregulates-transcription-of-brca1-in-neurons
#7
Jose F Moruno-Manchon, Edward C Koellhoffer, Jayakrishnan Gopakumar, Shashank Hambarde, Nayun Kim, Louise D McCullough, Andrey S Tsvetkov
The G-quadruplex is a non-canonical DNA secondary structure formed by four DNA strands containing multiple runs of guanines. G-quadruplexes play important roles in DNA recombination, replication, telomere maintenance, and regulation of transcription. Small molecules that stabilize the G-quadruplexes alter gene expression in cancer cells. Here, we hypothesized that the G-quadruplexes regulate transcription in neurons. We discovered that pyridostatin, a small molecule that specifically stabilizes G-quadruplex DNA complexes, induced neurotoxicity and promoted the formation of DNA double-strand breaks (DSBs) in cultured neurons...
September 12, 2017: Aging
https://www.readbyqxmd.com/read/28890163/single-stem-cell-imaging-and-analysis-reveals-telomere-length-differences-in%C3%A2-diseased-human-and-mouse-skeletal-muscles
#8
Elisia D Tichy, David K Sidibe, Matthew T Tierney, Michael J Stec, Maryam Sharifi-Sanjani, Harish Hosalkar, Scott Mubarak, F Brad Johnson, Alessandra Sacco, Foteini Mourkioti
Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres...
August 30, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28889809/leukocyte-telomere-length-and-personality-associations-with-the-big-five-and-type-d-personality-traits
#9
D Schoormans, J E Verhoeven, J Denollet, L van de Poll-Franse, B W J H Penninx
Backgrounds Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range. METHODS: Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls...
September 11, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28889732/effects-of-water-extract-of-curcuma-longa-l-roots-on-immunity-and-telomerase-function
#10
Min-Hsiung Pan, Jia-Ching Wu, Chi-Tang Ho, Vladimir Badmaev
Background Immunity and Longevity Methods A water extract of Curcuma longa (L.) [vern. Turmeric] roots (TurmericImmune™) standardized for a minimum 20 % of turmeric polysaccharides ukonan A, B, C and D was evaluated for its biological properties in in vitro tissue culture studies. Results The water extract of turmeric (TurP) exhibited induced-nitric oxide (NO) production in RAW264.7 macrophages. These results suggested the immunomodulatory effects of TurP. In addition, the polysaccharides up-regulated function of telomerase reverse transcriptase (TERT) equally to the phenolic compound from turmeric, curcumin...
May 12, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28888820/design-and-synthesis-of-2-phenylpyrimidine-coumarin-derivatives-as-anticancer-agents
#11
Na Lv, Ming Sun, Chen Liu, Jiabin Li
A series of 2-phenylpyrimidine coumarin derivatives with potential telomerase-inhibiting activity was designed and synthesized. All of the compounds were screened for antiproliferative activity against CNE2, KB, and Cal27 cell lines in vitro. The results showed that most of the derivatives had a favorable effect on resisting tumor cell proliferation; compound 13, 3-(4-amino-5-oxo-5H-chromeno[4,3-d]pyrimidin-2-yl)phenyl 4-(dimethylamino)benzenesulfonate, exhibited the best activity. Flow cytometry revealed that compound 13 can inhibit CNE2 proliferation...
August 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28886883/alternative-splicing-of-telomerase-catalytic-subunit-htert-generated-by-apoptotic-endonuclease-endog-induces-human-cd4-t-cell-death
#12
Dmitry D Zhdanov, Daria A Vasina, Vladimir A Grachev, Elena V Orlova, Valentina S Orlova, Marina V Pokrovskaya, Svetlana S Alexandrova, Nikolai N Sokolov
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4(+) and CD8(+) T lymphocytes...
September 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28883279/functional-analysis-of-protection-of-telomeres-1a-pot1a-in-regulation-of-hematopoietic-stem-cell-aging
#13
Kentaro Hosokawa, Ben D Macarthur, Yoshiko Ikushima, Hirofumi Toyama, Yoshikazu Masuhiro, Shigemasa Hanazawa, Toshio Suda, Fumio Arai
Repeated cell divisions induce DNA damage accumulation, which impairs stem cell function during aging. However, the general molecular mechanisms by which this occurs remain unclear. Herein, we show that the expression of protection of telomeres 1a (Pot1a), a component of shelterin, is crucial for prevention of telomeric DNA damage response (DDR) and maintenance of hematopoietic stem cell (HSC) activity during aging. We observed that HSCs express high levels of Pot1a during development, and this expression declines with aging...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28882819/cardiomyocyte-specific-telomere-shortening-is-a-distinct-signature-of-heart-failure-in-humans
#14
Maryam Sharifi-Sanjani, Nicholas M Oyster, Elisia D Tichy, Kenneth C Bedi, Ofer Harel, Kenneth B Margulies, Foteini Mourkioti
BACKGROUND: Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. METHODS AND RESULTS: We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution...
September 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28877996/blm-and-slx4-play-opposing-roles-in-recombination-dependent-replication-at-human-telomeres
#15
Alexander P Sobinoff, Joshua Am Allen, Axel A Neumann, Sile F Yang, Monica E Walsh, Jeremy D Henson, Roger R Reddel, Hilda A Pickett
Alternative lengthening of telomeres (ALT) is a telomere lengthening pathway that predominates in aggressive tumors of mesenchymal origin; however, the underlying mechanism of telomere synthesis is not fully understood. Here, we show that the BLM-TOP3A-RMI (BTR) dissolvase complex is required for ALT-mediated telomere synthesis. We propose that recombination intermediates formed during strand invasion are processed by the BTR complex, initiating rapid and extensive POLD3-dependent telomere synthesis followed by dissolution, with no overall exchange of telomeric DNA...
September 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28859657/fto-associations-with-obesity-and-telomere-length
#16
REVIEW
Yuling Zhou, Brett D Hambly, Craig S McLachlan
This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids...
September 1, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28855677/no-evidence-for-parental-age-effects-on-offspring-leukocyte-telomere-length-in-free-living-soay-sheep
#17
H Froy, E J Bird, R V Wilbourn, J Fairlie, S L Underwood, E Salvo-Chirnside, J G Pilkington, C Bérénos, J M Pemberton, D H Nussey
In humans, the effect of paternal age at conception (PAC) on offspring leukocyte telomere length (LTL) is well established, with older fathers thought to pass on longer telomeres to their offspring in their sperm. Few studies have looked for PAC effects in other species, but it has been hypothesised that the effect will be exacerbated in polygamous species with higher levels of sperm competition and production. We test for maternal (MAC) and paternal age at conception effects on offspring LTL in Soay sheep, a primitive breed experiencing strong sperm competition...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855279/telomere-length-dynamics-in-early-life-the-blood-and-muscle-model
#18
Sanjeev Sabharwal, Simon Verhulst, George Guirguis, Jeremy D Kark, Carlos Labat, Natalie E Roche, Kristina Martimucci, Krunal Patel, Debra S Heller, Masayuki Kimura, Donald Chuang, Anne Chuang, Athanase Benetos, Abraham Aviv
Telomere length (TL) trajectories in somatic tissues during human growth and development are poorly understood. We examined a blood-and-muscle model during early life, focusing on TL trajectories in leukocytes, representing the highly proliferative hematopoietic system, and skeletal muscle, a minimally proliferative tissue. Leukocyte TL (LTL) and skeletal muscle TL (MTL) were measured in 28 fetuses and 73 children. LTL and MTL were highly variable across individuals (sd: fetal LTL = 0.72 kb, MTL = 0.72 kb; children LTL = 0...
August 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28844059/do-donors-matter-short-telomeres-and-survival-after-lung-transplant
#19
EDITORIAL
Emily S Clausen, Laurie D Snyder
No abstract text is available yet for this article.
August 26, 2017: Thorax
https://www.readbyqxmd.com/read/28837806/rhodospirillum-rubruml-asparaginase-targets-tumor-growth-by-a-dual-mechanism-involving-telomerase-inhibition
#20
Dmitry D Zhdanov, Vadim S Pokrovsky, Marina V Pokrovskaya, Svetlana S Alexandrova, Mikhail A Eldarov, Dmitry V Grishin, Marsel M Basharov, Yulia A Gladilina, Olga V Podobed, Nikolai N Sokolov
Rhodospirillum rubruml-asparaginase mutant RrA E149R, V150P, F151T (RrA) was previously identified to down-regulate telomerase activity along with catalyzing the hydrolysis of l-asparagine. The aim of this study was to define the effect of prolonged RrA exposure on telomerase activity, maintenance of telomeres and proliferation of cancer cells in vitro and in vivo. RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT...
October 14, 2017: Biochemical and Biophysical Research Communications
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