Gabriele Saretzki

Summary

Affiliation: University of Newcastle
Country: UK

Publications

  1. pmc Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis
    Chatchawan Singhapol
    Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom
    PLoS ONE 8:e52989. 2013
  2. ncbi request reprint Telomerase, mitochondria and oxidative stress
    Gabriele 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
  3. ncbi request reprint Replicative aging, telomeres, and oxidative stress
    Gabriele Saretzki
    Department of Gerontology, University of Newcastle, Newcastle upon Tyne NE6 4BE, United Kingdom
    Ann N Y Acad Sci 959:24-9. 2002
  4. ncbi request reprint Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells
    Gabriele Saretzki
    Crucible Lab, Institute of Human Genetics, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom
    Stem Cells 26:455-64. 2008
  5. ncbi request reprint Telomerase inhibition as cancer therapy
    Gabriele Saretzki
    SCMS Gerontology, Institute of Ageing and Health, Newcastle University, General Hospital, NE4 6BE, Newcastle upon Tyne, UK
    Cancer Lett 194:209-19. 2003
  6. ncbi request reprint Cellular senescence in the development and treatment of cancer
    Gabriele 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
  7. doi request reprint Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress
    Shaheda Ahmed
    Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
    J Cell Sci 121:1046-53. 2008
  8. pmc Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence
    Joao 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
  9. pmc Adult-onset, short-term dietary restriction reduces cell senescence in mice
    Chunfang 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
  10. ncbi request reprint Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span
    Carmen 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

Collaborators

Detail Information

Publications39

  1. pmc Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis
    Chatchawan 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...
  2. ncbi request reprint Telomerase, mitochondria and oxidative stress
    Gabriele 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...
  3. ncbi request reprint Replicative aging, telomeres, and oxidative stress
    Gabriele 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...
  4. ncbi request reprint Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells
    Gabriele 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...
  5. ncbi request reprint Telomerase inhibition as cancer therapy
    Gabriele 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...
  6. ncbi request reprint Cellular senescence in the development and treatment of cancer
    Gabriele 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...
  7. doi request reprint Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress
    Shaheda 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...
  8. pmc Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence
    Joao 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...
  9. pmc Adult-onset, short-term dietary restriction reduces cell senescence in mice
    Chunfang 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
    ....
  10. ncbi request reprint Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span
    Carmen 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...
  11. ncbi request reprint 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...
  12. pmc 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...
  13. doi request reprint Human induced pluripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cells
    Lyle 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...
  14. ncbi request reprint 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 progenitors
    Katarzyna 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...
  15. pmc Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease
    Yan 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...
  16. pmc A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations
    Conor 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...
  17. pmc Feedback between p21 and reactive oxygen production is necessary for cell senescence
    Joao 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...
  18. ncbi request reprint Immortalisation of human ovarian surface epithelium with telomerase and temperature-sensitive SV40 large T antigen
    Barry 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...
  19. ncbi request reprint MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress
    Gabriele Saretzki
    Institute of Aging and Health, Newcastle University, Newcastle upon Tyne NE4 6BE, UK
    Aging Cell 2:141-3. 2003
  20. doi request reprint 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 progenitors
    Sun 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...
  21. ncbi request reprint Tumour-cell apoptosis after cisplatin treatment is not telomere dependent
    Jessie 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...
  22. ncbi request reprint The role of telomeres in Etoposide induced tumor cell death
    Jessie 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...
  23. ncbi request reprint A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell cycle dynamics, and in vitro differentiation
    Chunbo 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...
  24. ncbi request reprint TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts
    Torsten 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
    ....
  25. ncbi request reprint Telomerase as a promising target for human cancer gene therapy
    Gabriele 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...
  26. pmc Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice
    Satomi 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. ..
  27. pmc Chronic inflammation induces telomere dysfunction and accelerates ageing in mice
    Diana 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. ..
  28. ncbi request reprint hTERT gene dosage correlates with telomerase activity in human lung cancer cell lines
    Gabriele 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...
  29. ncbi request reprint Telomere shortening in human fibroblasts is not dependent on the size of the telomeric-3'-overhang
    Barbara Keys
    Henry Wellcome Biogerontology Laboratory, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Aging Cell 3:103-9. 2004
    ....
  30. ncbi request reprint Immediate and gradual gene expression changes in telomerase over-expressing fibroblasts
    Darren 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...
  31. pmc The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families
    Helen 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...
  32. ncbi request reprint Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening
    Violeta Serra
    Institute of Pathology and Research Laboratory Cardiology, Charite Hospital, D 10098 Berlin, Germany
    J Biol Chem 278:6824-30. 2003
    ....
  33. ncbi request reprint A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio 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...
  34. ncbi request reprint A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation
    Lyle Armstrong
    School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, UK
    Mech Dev 121:1509-22. 2004
    ....
  35. ncbi request reprint Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cells
    Gabriele 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
    ....
  36. ncbi request reprint Premature senescence of mesothelial cells is associated with non-telomeric DNA damage
    Krzysztof 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...
  37. ncbi request reprint Endogenous and ectopic expression of telomere regulating genes in chicken embryonic fibroblasts
    Georgios 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...
  38. ncbi request reprint Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart
    Nedime 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...
  39. pmc The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo
    Andre 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...