Genomes and Genes
Affiliation: University of Newcastle
- Extra-telomeric functions of human telomerase: cancer, mitochondria and oxidative stressG Saretzki
Institute for Ageing and Health, Campus for Ageing and Vitality Edwardson Building, Newcastle upon Tyne, NE4 5PL, UK
Curr Pharm Des 20:6386-403. 2014..Understanding these different mechanisms and their complexity in cancer cells might help to design more effective cancer therapies in the future...
- Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosisChatchawan Singhapol
Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom
PLoS ONE 8:e52989. 2013..We suggest that this decrease of oxidative stress might be a possible cause for high stress resistance of cancer cells and could be especially important for cancer stem cells...
- Cellular senescence in the development and treatment of cancerGabriele Saretzki
Crucible Laboratory, Institute for Ageing and Health, Newcastle University, International Centre for Life, Bioscience Centre, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
Curr Pharm Des 16:79-100. 2010..This review focuses on the basic mechanisms and recent advances for the induction of senescence as a potential cancer therapy and discusses the potential for a clinical application...
- Telomerase, mitochondria and oxidative stressGabriele Saretzki
Crucible Laboratory, Institute for Ageing and Health, International Centre for Life, Bioscience Centre, Central Parkway, Newcastle upon Tyne, United Kingdom
Exp Gerontol 44:485-92. 2009..This review summarises briefly our knowledge about extra-telomeric functions of telomerase and discusses the potential significance of its mitochondrial localisation...
- Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cellsGabriele Saretzki
Crucible Lab, Institute of Human Genetics, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom
Stem Cells 26:455-64. 2008..These results confirm earlier data obtained during mouse embryonic stem cell differentiation and are in accordance with evolutionary predictions...
- Telomerase inhibition as cancer therapyGabriele Saretzki
SCMS Gerontology, Institute of Ageing and Health, Newcastle University, General Hospital, NE4 6BE, Newcastle upon Tyne, UK
Cancer Lett 194:209-19. 2003..It has been demonstrated that telomerase may be involved in triggering apoptosis, but the underlying molecular mechanism remains unclear...
- Replicative aging, telomeres, and oxidative stressGabriele Saretzki
Department of Gerontology, University of Newcastle, Newcastle upon Tyne NE6 4BE, United Kingdom
Ann N Y Acad Sci 959:24-9. 2002..These data suggest that parameters that characterise replicative senescence in vitro offer potential for understanding of, and intervention into, the aging process in vivo...
- Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescenceJoao F Passos
Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, United Kingdom
PLoS Biol 5:e110. 2007..X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan...
- Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stressShaheda Ahmed
Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
J Cell Sci 121:1046-53. 2008..We propose protection of mitochondria under mild stress as a novel function of TERT...
- Mitochondrial dysfunction and cell senescence: cause or consequence?Joao F Passos
Henry Wellcome Laboratory for Biogerontology Research, Institute for Aging and Health, University of Newcastle, Newcastle upon Tyne, United Kingdom
Rejuvenation Res 9:64-8. 2006..Moreover, we suggest that this process might be more complex than originally formulated, because variations in nuclear gene expression involved in mitochondrion nucleus cross-talk are observed in both senescence and immortalization...
- Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life spanCarmen Martin-Ruiz
Henry Wellcome Biogerontology Laboratory, School of Clinical Medical Sciences, University of Newcastle, General Hospital, Newcastle NE4 6BE, United Kingdom
J Biol Chem 279:17826-33. 2004..The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening...
- Adult-onset, short-term dietary restriction reduces cell senescence in miceChunfang Wang
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
Aging (Albany NY) 2:555-66. 2010....
- Human induced pluripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cellsLyle Armstrong
Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom
Stem Cells 28:661-73. 2010..Together our data suggest that, during the reprogramming process, certain cellular mechanisms are in place to ensure that hiPSC are provided with the same defense mechanisms against accumulation of ROS as the hESC...
- DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?Joao F Passos
Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne NE4 6BE, UK
Nucleic Acids Res 35:7505-13. 2007..Together, these data suggest a self-amplifying cycle between mitochondrial and telomeric DNA damage during cellular senescence...
- Feedback between p21 and reactive oxygen production is necessary for cell senescenceJoao F Passos
Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
Mol Syst Biol 6:347. 2010..These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype...
- Brief report: a human induced pluripotent stem cell model of cernunnos deficiency reveals an important role for XLF in the survival of the primitive hematopoietic progenitorsKatarzyna Tilgner
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom NESCI, Newcastle University, Newcastle, United Kingdom
Stem Cells 31:2015-23. 2013..Together, our findings highlight the importance of NHEJ-mediated-DNA repair in the maintenance of a pristine pool of hematopoietic progenitors during human embryonic development...
- Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous diseaseYan Jiang
Institute of Genetic Medicine, Newcastle University, Newcastle, UK
Stem Cells 30:599-611. 2012..Together these results suggest that CGD-patient-specific iPSC lines represent an important tool for modeling CGD disease phenotypes, screening candidate drugs, and the development of gene therapy...
- A stochastic step model of replicative senescence explains ROS production rate in ageing cell populationsConor Lawless
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
PLoS ONE 7:e32117. 2012..We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence...
- MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stressGabriele Saretzki
Institute of Aging and Health, Newcastle University, Newcastle upon Tyne NE4 6BE, UK
Aging Cell 2:141-3. 2003
- Immortalisation of human ovarian surface epithelium with telomerase and temperature-sensitive SV40 large T antigenBarry R Davies
Department of Surgery, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
Exp Cell Res 288:390-402. 2003..OSE-C2 cells may be useful in studying the physiology and differentiation of human OSE cells and provide insight into the poorly understood earliest stages of epithelial ovarian cancer...
- The role of telomeres in Etoposide induced tumor cell deathJessie Jeyapalan
Henry Wellcome Biogerontology Laboratory, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
Cell Cycle 3:1169-76. 2004..However, upregulation of telomerase might be part of an attempted adaptative response, which protects cells by a mechanism that might be independent of telomere length maintenance...
- A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell cycle dynamics, and in vitro differentiationChunbo Yang
North East Institute for Stem Cell Research, Newcastle upon Tyne NE1 3BZ, United Kingdom
Stem Cells 26:850-63. 2008..Our results indicate for the first time an important role for TERT in the maintenance of human ESC pluripotency, cell cycle regulation, and in vitro differentiation capacity...
- Brief report: human pluripotent stem cell models of fanconi anemia deficiency reveal an important role for fanconi anemia proteins in cellular reprogramming and survival of hematopoietic progenitorsSun K Yung
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
Stem Cells 31:1022-9. 2013..Together these data highlight the critical requirement for FA proteins in survival of hematopoietic progenitors, cellular reprogramming, and maintenance of genomic stability...
- Tumour-cell apoptosis after cisplatin treatment is not telomere dependentJessie C Jeyapalan
Henry Wellcome Biogerontology Laboratory, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
Int J Cancer 118:2727-34. 2006..X at nontelomeric sites. Interstitial DNA damage appears to be more important than telomere loss or telomeric damage as inducer of the signal pathway towards apoptosis and/or growth arrest in cisplatin-treated tumour cells...
- TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblastsTorsten Richter
Henry Wellcome Biogerontology Laboratory and Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, University of Newcastle upon Tyne, UK
Mech Ageing Dev 128:340-5. 2007....
- Telomerase as a promising target for human cancer gene therapyGabriele Saretzki
Gerontology, Institute of Ageing and Health, Newcastle University, UK
Drugs Today (Barc) 39:265-76. 2003..Other important strategies are the use of telomerase promoters for the application of toxic or pro-apoptotic drugs into human cancer cells or the use of immunological properties of the telomerase enzyme for possible cancer therapies...
- Chronic inflammation induces telomere dysfunction and accelerates ageing in miceDiana Jurk
Institute for Ageing and Health, Newcastle University, NE4 5PL, UK
Nat Commun 2:4172. 2014..These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor. ..
- Low abundance of the matrix arm of complex I in mitochondria predicts longevity in miceSatomi Miwa
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
Nat Commun 5:3837. 2014..We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity. ..
- Telomere shortening in human fibroblasts is not dependent on the size of the telomeric-3'-overhangBarbara Keys
Henry Wellcome Biogerontology Laboratory, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
Aging Cell 3:103-9. 2004....
- hTERT gene dosage correlates with telomerase activity in human lung cancer cell linesGabriele Saretzki
Deptartment of Gerontology, University of Newcastle, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK
Cancer Lett 176:81-91. 2002..We found a significant correlation between hTERT gene dosage, hTERT mRNA expression and telomerase activity. Imbalances of chromosome 5p may exert functionally relevant hTERT gene dosage effects in human lung cancer...
- Immediate and gradual gene expression changes in telomerase over-expressing fibroblastsDarren J Daniels
Institute for Ageing and Health, Newcastle University, International Centre for Life, Central Parkway, UK
Biochem Biophys Res Commun 399:7-13. 2010..These changes should be taken into account when these cells are used as functional models or for regenerative purposes...
- Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotypeNouf Al-Ajmi
Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
Exp Gerontol 58:113-9. 2014..We conclude that whilst shortened telomeres mimic some aspects of haematopoietic ageing, both shortened telomeres and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction. ..
- The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple familiesHelen A L Tuppen
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK
Brain 133:2952-63. 2010..Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes...
- A DNA damage checkpoint response in telomere-initiated senescenceFabrizio d'Adda di Fagagna
1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
Nature 426:194-8. 2003..Thus, we propose that telomere-initiated senescence reflects a DNA damage checkpoint response that is activated with a direct contribution from dysfunctional telomeres...
- A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiationLyle Armstrong
School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, UK
Mech Dev 121:1509-22. 2004....
- Endogenous and ectopic expression of telomere regulating genes in chicken embryonic fibroblastsGeorgios Michailidis
Institute of Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
Biochem Biophys Res Commun 335:240-6. 2005..These data indicate that the human TERT is incompatible with the avian telomere maintenance apparatus and suggest the functioning of a species specific telomere system in the avian...
- Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpartNedime Serakinci
Department of Human Genetics, University of Aarhus, Aarhus, Denmark
Exp Cell Res 313:1056-67. 2007..The TERT-immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps...
- Premature senescence of mesothelial cells is associated with non-telomeric DNA damageKrzysztof Ksiazek
Department of Pathophysiology, University of Medical Sciences, Swiecickiego 6, 60781 Poznan, Poland
Biochem Biophys Res Commun 362:707-11. 2007..These results may indicate that premature senescence of HPMCs is largely related to oxidative stress-induced DNA damage in non-telomeric regions of the genome...
- Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shorteningVioleta Serra
Institute of Pathology and Research Laboratory Cardiology, Charite Hospital, D 10098 Berlin, Germany
J Biol Chem 278:6824-30. 2003....
- Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cellsGabriele Saretzki
Henry Wellcome Laboratory for Biogerontology, Newcastle General Hospital, University of Newcastle upon Tyne, Newcastle upon Tyne NE4 6BE, UK
Stem Cells 22:962-71. 2004....
- The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivoAndre Lechel
Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany
EMBO Rep 6:275-81. 2005..Our data provide experimental evidence that induction of senescence or apoptosis in vivo depends on the cellular level of telomere dysfunction and differentially on p53 gene function...