Staff Profile
Dr Gabriele Saretzki
Lecturer in Ageing Research
- Email: gabriele.saretzki@ncl.ac.uk
- Telephone: +44 (0) 191 208 1214
- Fax: +44 (0) 191 208 1101
- Address: Biosciences Institute and Newcastle University Institute for Ageing,Campus for Ageing and Vitality,
Edwardson Building,
Newcastle University
Newcastle upon Tyne
NE4 5PL, UK
Introduction
I am a cellular biologist with research experience in the fields of ageing, senescence and cancer for more than 20 years. Most of my work focuses on telomerase/TERT and oxidative stress as well as DNA damage. I am interested in the role of oxidative stress and mitochondria in the ageing process and cellular senescence. My group has shown a protective role for telomerase/TERT for mitochondrial function and decrease of oxidative stress in various in vitro systems (Ahmed et al., 2008, Singhapol et al., 2013). We recently demonstrated a potential protective role of neuronal TERT moving into mitochondria in neurodegenerative diseases on brains from patients with Alzheimers' disease (Spilsbury et al., 2015). We also used in vivo models of TERT knockout mice under dietary restriction and rapamycin treatment as well as for transduction of mutated tau to analyse this protective function of telomerase/TERT in mitochondria and found a role for mitochondrial TERT in brain ageing and neurodegenerative diseases in vivo. We have recently performed preclinical experiments using telomerase activators on a mouse model of Parkinson's disease with very encouraging results which identify telomerase activation as a strategic therapy for neurodegenerative diseases.
Background
I am a cellular biologist with a broad range of experience, interests and technical skills. My main scientific career has been devoted to investigating the involvement of oxidative stress, telomeres and telomerase in processes connected to cellular ageing, cancer, stem cells as well as more recently, brain ageing. For my doctoral research, I worked in molecular virology, expressing surface domains of the hepatitis B virus in different microorganisms for application as vaccines against Hepatitis B. During that time I prepared and taught a half year laboratory course in general and molecular genetics. For my first post-doc years I worked in diagnostic pathology, introducing new methods like in-situ hybridization, immunohistochemistry and PCR into pathological diagnostics. In the context of cancer pathology, I analysed translocations ,microsatellite instabilities, losses of heterozygosity [3, 9] and gene amplifications .
For the last 20 years my main research interests have been devoted to the role of oxidative stress, telomeres and telomerase in ageing, cancer and stem cells. In close collaboration with other scientists I have investigated the role of senescence, oxidative stress and telomeres in the basic biology of ageing as well as related clinical questions. Our current findings about a potential role of non-canonical telomerase functions of the telomerase protein TERT in mitochondria of brain during dietary restriction (DR) and rapamycin treatment got me into the area of brain ageing and neurodegenerative diseases. Our recent preclinical experiments on a mouse model of Parkinson's disease (PD) using telomerase activators to boos TERT levels showed a substantial improvement of PD related behaviours such as balance and gait as well as a significant decrease in total, phosphorylated and aggregated alpha-synuclein. These results suggest that increased telomerase might activate protein degradation mechanisms such as autophagy.
Roles and Responsibilities
•Editorial member of “Biogerontology” from 2002-2012, Associated Editor for BMC Biology since 2009, Oxidative Medicine and Longevity as well as PLoS one since 2011, I edited 2 special issues on the role of telomeres and telomerase in ageing and cancer for the International journal of molecular sciences.
•Reviewer for different funding bodies (BBSRC, Wellcome, MRC, Singapore Medical Academy etc) and various journals :Mechanism of Aging and Development, Ageing Cell, Experimental Gerontology,Biogerontology,Experimental Cell Research,International Journal of Cancer,Molecular Cancer,Reviews in Medical Chemistry, Cancer Letters, PLos one, BMC, NAR and many more
Qualifications
- 1977-1982 Diploma (MSc) in Biology/Genetics, Department of Genetics and Selection, University of St. Petersburg, Russia: “Characterisation of recessive suppressor mutants depending on cyclohexamide in S. cerevisiae”(magna cum laude)
- 1986-1990 PhD in Molecular Biology, Department of Genetics, Humboldt University Berlin, Germany: "Expression of surface antigens of Hepatitis B virus in bacteria and yeast” (magna cum laude), Supervisor Prof. T. Bőrner
- 1994-1995 Postdoctoral Research Fellowship, Institute of Pathology of the Technical University and Research Institute (GSF), Munich, Germany
- 7-9/1996 Research Fellow/ Visiting Scientist, Geron Corp. Menlo Park, CA, USA
Previous Positions
- 1982-86 Junior Research Associate, Department of Genetics, Humboldt-University Berlin, Germany
- 1986-1989 PhD student, Department of Genetics, Humboldt- University Berlin, Germany
- 1989-99 Research Associate, Institute of Pathology, Charite’, Humboldt-University Berlin
- 1999-2000 Research Associate, Department of Gynecology, University Hospital, Freiburg, Germany
- 2001-2002 Senior Research Associate, Gerontology, Institute for Ageing and Health, University of Newcastle, U.K.
- 2002-present Lecturer, Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Institute for Cellular and Molecular Biology, Newcastle University, Newcastle upon Tyne, NE4 5PLU.K.
Honours and Awards
•1994-1995 Research Fellowship Jung-Foundation for Science, Hamburg, Germany
•1996 (3 month) Research Fellowship Geron Corp. Menlo Park, CA
Languages
German, English, Russian,
Informal Interests
I love cats and animals, I support WWF, Animal Asia and the RSPCA, I am interested in environmental issues, I like sports (windsurfing, climbing, dancing) and travelling.
Research Interests
My research interests are devoted to the role of telomerase in ageing and cancer and under oxidative stress. I focus particularly on non-telomeric and non-canonical roles of telomerase. We and others have found that telomerase shuttles from the nucleus to mitochondria under oxidative stress. My group was the first to describe a protective role of telomerase and its protein part TERT onto mitochondria (Ahmed et al., 2008). We recently found that cancer cells protect themselfs from external stress by mitochondrial localisation of telomerase which decreases nuclear damage and apoptosis and is therefore a pro-survival mechanism (Singhapol et al., 2013). Since adult neurons do not express telomerase activity but still express TERT, the protein part of telomerase, we demonstrated recently that this could protect neurons from oxidative damage and neurodegenerative agents such as hyperphosphorylated tau (Spilsbury et al., 2015). We also used embryonic mouse neurons from telomerase/TERT deficient as well as wild type mice and transduced them with lentiviruses against a mutant (P301L) tau protein and showed more oxidative stress and lipid peroxidation in neurons lacking TERT compared to wild type neurons (Spilsbury et al., 2015). Thus TERT seems to protects neurons against hyperphosphorylated tau protein which induces neurodegeneration in the context of Alzheimer's disease and other tauopaties. We propose that boosting TERT levels in the brain using known telomerase activators could help prevent or ameliorate neurodegenerative diseases and dementia related to it. I have introduced new methods for measuring cognitive properties such as Barnes maze (learning and memory) and locomotor tests for mice in our institute.
I am also interested in the mechanisms of stem cell ageing and senescence and investigate the role of telomeres, telomerase and oxidative stress in those. I recently got interested and involved in nutritional aspects of ageing.
Other Expertise
•regular reviews for different funding bodies (UK: BBSRC, Wellcome, MRC, Singapore Medical academy).
•Reviewer for different journals: PLoS one, Mechanism of Aging and Development,
Ageing Cell, Experimental Gerontology, Biogerontology, Experimental Cell Research, International Journal of Cancer, Molecular Cancer, Cancer Letters
Current Research
I have various ongoing research collaborations, including work on human iPS cells and nutritional aspects analysing fat and differentiation adipocytes in vitro which we treat with lipidogenic media and test nutritional foof components such as nitrate and chicoric acid for their beneficial effects with the aim of uncovering the underlying mechanisms..
Research Roles
I am a PI and Lecturer in Ageing Research at the Institute for Cell and Molecular Biosciences and a member of the Newcastle Institute for Ageing.
Postgraduate Supervision
I have currently 2 PhD students. In addition, I have regular national and international undergraduate and graduate students and scientists who work in placements, masters, undergraduate projects and summer student projects and perform scientific visits to my lab.
Esteem Indicators
speaker and session chair for various national and international meetings on Ageing etc
Funding
1997-2000, Cancer Society Berlin: Telomerase combination therapy £200k
•1988-1999 Humboldt University Berlin, Medical Faculty (Charite) Research fund: “Diagnostic potential of telomerase activity for early stages of cervical intraepithelial lesions”, £10k
•2001-2003 Medical Research Council, U.K.: “Telomerase inhibition in prostate cancer” (part of Cooperative Grant on Prostate Cancer) 1/02 - 12/03, £140k
•2003-2004: National Health Trust (Special Trustees): “Mechanism of fast apoptosis induction by targeting telomerase with an anti-hTERT ribozyme in human cancer cells”, £30K
•2003-2008 Co- Investigator for Research into Ageing (now Age UK) Programme “Human cell replicative senescence as stress response: Role of telomeres” , £398K
•2005-2010 named researcher on BBSRC Grant Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN) for Biogerontology, Institute for Ageing and Health, School of Clinical medical Sciences, University Newcastle, £6.7million
•2005-2006 Co-Investigator for Grant of the National Health Trust (Special Trustees): “The Role of Oxidative Stress in the Phenotypic and Functional Change Occurring in Lung Epithelial Cells undergoing Epithelial to Mesenchymal Transition (EMT)”, £50K
•2005-2008 Co-Investigator for Cancer UK studentship “Identification and validation of candidate genes involved in differentiation of human prostate epithelial stem cells” £70k
2008-2009: co-applicant : X-ray research irradiation system, Ref BB/F010966/1, £141849.91, BBSRC,
2009-2011, co-applicant on grant from "Wellbeing of women", The role of the identified regulators of cell fate (RCF) and metastasis inducing proteins (MIP) in endometrial stem/progenitor cells (SPC) in endometriosis. £149K
2009-2012, co-applicant with Prof. Majlinda Lako “Investigating early haematopoietic development in ligase IV and XLF patients using induced pluripotent stem cells”. £165.845, Leukaemia Research Fund.
2008-2012, PhD studentship, £78K from Thai government
2009-2012 PhD studentship, 50K, BBSRC
2010-2013, PhD studentship, 50K from Biomedical Research Centre at Newcastle University
2012-2013: Dunhill Medical Trust Srendipity award on the role of mitochondrial Telomerase in the protection from tau related neurodegeneration (76.5K)
1-6/2015: MRC confidence in concept funding (13.5K) for testing beneficial effects on pathology and brain function in PD line D mice using telomerase activators.
Patents
von Zglinicki T, Ludwig A, Saretzki G “Ribozymes targeting the catalytic subunit of human telomerase (hTERT)”, German Patent # 199 03 961.5, International patent PCT/DE 100 03
356
Undergraduate Teaching
1984-89 Mentor for undergraduates in molecular biology, Institute of Biology, Humboldt-University Berlin
1984-1985 Conception and teaching of a laboratory course “Molecular Genetics” for undergraduate students in Biology
1985-87 Lectures in Molecular Biology, Institute of Biology, Humboldt-University Berlin
since 2003- regular project supervisor for undergraduate stage 3 projects
since 2010- teaching in the new undergraduate model "Biology of Ageing"
Annual supervision of summer students
Postgraduate Teaching
1993-1999 Supervision of MSc, PhD and MD students, Institute of Pathology, Humboldt-University Berlin
1996 - 1999 Lectures series “ Molecular Medicine and Tumours” , Institute of Pathology, Charite’, Humboldt-University Berlin
since 2001: Supervision of 10 graduate students and projects, at the Institute for Ageing and Health, Newcastle University, supervision of masters, MRES and MPHIL students
since 2009-teaching in the MRes course "Ageing" at Newcastle University
since 2011: teaching in masters course "Stem cells and regenerative medicine"
- Martin-Ruiz C, Williams-Gray CH, Yarnall AJ, Boucher JJ, Lawson RA, Wijeyekoon RS, Barker RA, Kolenda C, Parker C, Burn DJ, Von Zglinicki T, Saretzki G. Senescence and inflammatory markers for predicting clinical progression in Parkinson's disease-the ICICLE-PD study. Journal of Parkinson's Disease 2020, 10(1), 193-206.
- Chan D, Martin-Ruiz C, Saretzki G, Neely D, Qiu W, Kunadian V. The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome. PLoS ONE 2020, 15(1), e0227616.
- da Silva PFL, Ogrodnik M, Kucheryavenko O, Glibert J, Miwa S, Cameron K, Ishaq A, Saretzki G, Nagaraja-Grellscheid S, Nelson G, von Zglinicki T. The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell 2019, 18(1), e12848.
- Ishaq A, Schroder J, Edwards N, von Zglinicki T, Saretzki G. Dietary restriction ameliorates age-related increase in DNA damage, senescence and inflammation in mouse adipose tissuey. Journal of Nutrition, Health and Aging 2018, 22(4), 555-561.
- Sanchis DM, Xu Y, Taheem D, Yu M, Tilgner K, Barta T, Gassner K, Anyfanftis G, Wan T, Elango R, Alharthi S, Elharouni AA, Pryzborski S, Adam S, Saretzki G, Samarasinghe S, Armstrong L, Lako M. iPSC modelling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors. Cell Death & Disease 2018, 9, 128.
- Ishaq A, Dufor D, Cameron K, von Zglinicki T, Saretzki G. Metabolic memory of dietary restriction ameliorates DNA damage and adipocyte size in mouse visceral adipose tissue. Experimental Gerontology 2018, 113, 228-236.
- Richardson G, Sage A, Bennaceur K, Al Zhrany N, Coelho-Lima J, Dookun E, Draganova L, Saretzki G, Breault D, Mallat Z, Spyridopoulos I. Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells. Arteriosclerosis, Thrombosis, and Vascular Biology 2018, 38(6), 1283-1296.
- Saretzki Gabriele. Telomeres, Telomerase and Ageing. In: J. Robin Harris, Viktor I. Korolchuk, ed. Biochemistry and Cell Biology of Ageing: Part I Biomedical Science. Singapore: Springer, 2018, pp.221-308.
- Hallam D, Collin j, Bojic S, Chichagova V, Buskin A, Xu Y, Lafage L, Otten EG, Anyfantis G, Mellough C, Przyboski S, Alhart S, Korolchuk V, Lotery A, Saretzki G, McKibbin M, Armstrong L, Steel D, Kavanagh D, Lako M. An iPSC patient specific model of CFH (Y402H) polymorphism displays characteristic features of AMD and indicates a beneficial role for UV light exposure. Stem Cells 2017, 35(11), 2305-2320.
- Chichagova V, Hallam D, Collin J, Buskin A, Saretzki G, Armstrong L, Yu-Wai-Man P, Lako M, Steel DH. Human iPSC disease modelling reveals functional and structural defects in retinal pigment epithelial cells harbouring the m.3243A>G mitochondrial DNA mutation. Scientific Reports 2017, 7, 12320.
- Miwa S, Saretzki G. Telomerase and mTOR in the brain: The mitochondria connection. Neural Regeneration Research 2017, 12(3), 358-361.
- Miwa S, Czapiewski R, Wan TF, Bell A, Hill KN, von Zglinicki T, Saretzki G. Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria. Aging 2016, 8(10), 2551-2567.
- Ashor AW, Chowdhury S, Oggioni C, Qadir O, Brandt K, Ishaq A, Mathers JC, Saretzki G, Siervo M. Inorganic Nitrate Supplementation in Young and Old Obese Adults Does Not Affect Acute Glucose and Insulin Responses but Lowers Oxidative Stress. Journal of Nutrition 2016, 146(11), 2224-2232.
- Correia-Melo C, Marques FDM, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SWG, Czapiewski R, Greaves L, Nelson G, Bohlooly-Y M, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO Journal 2016, 35(7), 724-742.
- Ishaq A, Hanson PS, Morris CM, Saretzki G. Telomerase Activity is Downregulated Early During Human Brain Development. Genes 2016, 7(6), 27.
- Zhu L, Gomez-Duran A, Saretzki G, Jin S, Tilgner K, Melguzo-Sanchis D, Anyfantis G, Al-Aama J, Vallier L, Chinnery P, Lako M, Armstrong L. The mitochondrial protein CHCHD2 primes the differentiation potential of human induced pluripotent stem cells to neuroectodermal lineages. Journal of Cell Biology 2016, 215(2), 187-202.
- Anderson R, TualChalot S, Redgrave R, Dodds R, Owens WA, Saretzki G, Arthur H, vonZglinicki T, Passos JF, Richardson GD. The role of cardiomyocyte senescence and regeneration in Ageing. In: British Microcirculation Society 66th Annual Meeting. 2016, Newcastle upon Tyne, UK: BMS.
- Kunadian V, Veerasamy M, Sinclair H, Batty J, Sharifpour M, Lima J, Neely D, Martin-Ruiz C, Saretzki G. Association of Telomere Length and Telomerase Activity with Clinical Parameters in Older Patients Undergoing Invasive Management Of non-ST Elevation Acute Coronary Syndrome. In: BCS annual conference. 2015, Manchester, UK: BMJ Group.
- Hallam DM, Wan T, Saretzki G. Dietary restriction mitigates age-related accumulation of DNA damage, but not all changes in mouse corneal epithelium. Experimental Gerontology 2015.
- Spilsbury A, Miwa S, Attems J, Saretzki G. The Role of Telomerase Protein TERT in Alzheimer's Disease and in Tau-Related Pathology In Vitro. Journal of Neuroscience 2015, 35(4), 1659-1674.
- Bennaceur K, Atwill M, Al Zhrany N, Hoffmann J, Keavney B, Breault D, Richardson G, von Zglinicki T, Saretzki G, Spyridopoulos I. Atorvastatin induces T cell proliferation by a telomerase reverse transcriptase (TERT) mediated mechanism. Atherosclerosis 2014, 236(2), 312-320.
- Jurk D, Wilson C, Passos J, Oakley F, Correia-Melo C, Greaves L, Saretzki G, Fox C, Lawless C, Anderson R, Hewitt G, Pender SLF, Fullard N, Nelson G, Mann J, van de Sluis B, Mann DA, von Zglinicki T. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nature Communications 2014, 5, 4172.
- Al-Ajmi N, Saretzki G, Miles C, Spyridopoulos I. Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbate the ageing phenotype. Experimental Gerontology 2014, 58, 113-119.
- Miwa S, Jow H, Baty K, Johnson A, Czapiewski R, Saretzki G, Treumann A, von Zglinicki T. Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice. Nature Communications 2014, 5, 3837.
- Tilgner K, Neganova I, Moreno-Gimeno I, Al-Aama JY, Burks D, Yung S, Singhapol C, Saretzki G, Evans J, Gorbunova V, Gennery A, Pryzborski S, Stojkovic M, Armstrong L, Jeggo P, Lako M. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors. Cell Death and Differentiation 2013, 20, 1089-1100.
- Tilgner K, Neganova I, Singhapol C, Saretzki G, Al-Aama JY, Evans J, Gorbunova V, Gennery A, Przyborski S, Stojkovic M, Armstrong L, Jeggo P, Lako M. 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. Stem Cells 2013, 31(9), 2015-2023.
- Yung SK, Tilgner K, Ledran MH, Habibollah S, Neganova I, Singhapol C, Saretzki G, Stojkovic M, Armstrong L, Przyborski S, Lako M. 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. Stem Cells 2013, 31(5), 1022-1029.
- Singhapol C, Pal D, Czapiewski R, Porika M, Nelson G, Saretzki GC. Mitochondrial Telomerase Protects Cancer Cells from Nuclear DNA Damage and Apoptosis. PLoS One 2013, 8(1), e52989.
- Lawless C, Jurk D, Gillespie CS, Shanley D, Saretzki G, von Zglinicki T, Passos JF. A Stochastic Step Model of Replicative Senescence Explains ROS Production Rate in Ageing Cell Populations. PLoS One 2012, 7(2), e32117.
- Siler U, Jiang Y, Cowley SA, Melguzo D, Tilgner K, Browne C, deWilton A, Pryzborski S, Saretzki G, James WS, Seger RA, Reichenbach J, Lako M, Armstrong L. Derivation and functional analysis of patient specific induced pluripotent stem cells (IPSCS) as an in vitro model of chronic granulomatous disease. In: 15th Biennial Meeting European Society for Immunodeficiency (ESID). 2012, Florence, Italy: Springer.
- Siler U, Jiang Y, Cowley SA, Melguzo D, Tilgner K, Browne C, Dewilton A, Pryzborski S, Saretzki G, James WS, Seger RA, Reichenbach J, Lako M, Armstrong L. Derivation and Functional Analysis of Patient Specific Induced Pluripotent Stem Cells as an In Vitro Model of Chronic Granulomatous Disease. In: 15th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). 2012, Philadelphia, Pennsylvania, USA: Nature Publishing Group.
- Jiang Y, Cowley SA, Siler U, Melguizo D, Tilgner K, Browne C, Dewilton A, Przyborski S, Saretzki G, James WS, Seger RA, Reichenbach J, Lako M, Armstrong L. Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease. Stem Cells 2012, 30(4), 599-611.
- Gorowiec MR, Borthwick LA, Parker SM, Kirby JA, Saretzki GC, Fisher AJ. Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-beta 1-dependent mechanism. Free Radical Biology & Medicine 2012, 52(6), 1024-1032.
- Tsolou A, Nelson G, Trachana V, Chondrogianni N, Saretzki G, von Zglinicki T, Gonos ES. The 19S proteasome subunit Rpn7 stabilizes DNA damage foci upon genotoxic insult. IUBMB Life 2012, 64(5), 432-442.
- Saretzki G. Telomerase and Oxidative Stress in Embryonic Stem Cells. In: Atwood, C, ed. Embryonic Stem Cells: The Hormonal Regulation of Pluripotency and Embryogenesis. Rijeka, Croatia: InTech, 2011, pp.357-362.
- Saretzki G. Telomerase beyond telomeres: New roles for an Old Enzyme. In: Gagnon, AN, ed. Telomerase: Composition, Functions and Clinical Implications (DNA: Properties and Modifications, Functions and Interactions, Recombination and Applications. Nova Science Publishers, Inc, 2011, pp.1-34.
- Wang CF, Maddick M, Miwa S, Jurk D, Czapiewski R, Saretzki G, Langie SAS, Godschalk RWL, Cameron K, von Zglinicki T. Adult-onset, short-term dietary restriction reduces cell senescence in mice. Aging 2010, 2(9), 555-566.
- Saretzki G. Cellular senescence in the development and treatment of cancer. Current Pharmaceutical Design 2010, 16(1), 79-100.
- Passos JF, Nelson G, Wang CF, Richter T, Simillion C, Proctor CJ, Miwa S, Olijslagers S, Hallinan J, Wipat A, Saretzki G, Rudolph KL, Kirkwood TBL, von Zglinicki T. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Molecular Systems Biology 2010, 6(1), 347.
- Armstrong L, Tilgner K, Saretzki G, Atkinson SP, Stojkovic M, Moreno R, Przyborski S, Lako M. Human Induced Pluripotent Stem Cell Lines Show Stress Defense Mechanisms and Mitochondrial Regulation Similar to Those of Human Embryonic Stem Cells. Stem Cells 2010, 28(4), 661-673.
- Daniels DJ, Clothier C, Swan DC, Saretzki G. Immediate and gradual gene expression changes in telomerase over-expressing fibroblasts. Biochemical and Biophysical Research Communications 2010, 399(1), 7-13.
- Tuppen HA, Hogan VE, He L, Blakely EL, Worgan L, Al-Dosary M, Saretzki G, Alston CL, Morris AA, Clarke M, Jones S, Devlin AM, Mansour S, Chrzanowska-Lightowlers ZMA, Thorburn DR, McFarland R, Taylor RW. The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families. Brain 2010, 133(10), 2952-2963.
- Büchner N, Altschmied J, Jakob S, Saretzki G, Haendeler J. Well-known signaling proteins exert new functions in the nucleus and mitochondria. Antioxidants and Redox Signaling 2010, 13(4), 551-558.
- Saretzki G. Telomerase, mitochondria and oxidative stress. Experimental Gerontology 2009, 44(8), 485-492.
- Yang C, Przyborski S, Cooke MJ, Zhang X, Stewart R, Anyfantis G, Atkinson SP, Saretzki GC, Armstrong L, Lako M. A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell cycle dynamics, and in vitro differentiation. Stem Cells 2008, 26(4), 850-863.
- Parker SM, Goriwiec MR, Borthwick LA, Johnson G, Ward C, Lordan JL, Corris PA, Saretzki GC, Fisher AJ. Airway epithelial cell senescence in the lung allograft. American Journal of Transplantation 2008, 8(7), 1544-1549.
- Saretzki G, Walter T, Atkinson S, Passos JF, Bareth B, Keith WN, Stewart R, Hoare S, Stojkovic M, Armstrong L, Von Zglinicki T, Lako M. Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells. Stem Cells 2008, 26(2), 455-464.
- Hapangama DK, Turner MA, Drury JA, Quenby S, Saretzki G, Martin-Ruiz C, Von Zglinicki T. Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length. Human Reproduction 2008, 23(7), 1511-1519.
- Ahmed S, Passos JF, Birket MJ, Beckmann T, Brings S, Peters HH, Birch-Machin MA, von Zglinicki TW, Saretzki GC. Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. Journal of Cell Science 2008, 121(7), 1046-1053.
- Passos J, Saretzki G, von Zglinicki T. DNA damage in telomeres and mitochondria during cellular senescence: Is there a connection?. Nucleic Acids Research 2007, 35(22), 7505-7513.
- Serakinci N, Christensen R, Graakjaer J, Cairney CJ, Keith WN, Alsner J, Saretzki G, Kolvraa S. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. Experimental Cell Research 2007, 313(5), 1056-1067.
- Passos JF, Saretzki G, Ahmed S, Nelson G, Richter T, Peters H, Wappler I, Birket MJ, Harold G, Schaeuble K, Birch-Machin MA, Kirkwood TBL, von Zglinicki T. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biology 2007, 5(5), 1138-1151.
- Ksiazek K, Passos JF, Olijslagers S, Saretzki G, Martin-Ruiz C, von Zglinicki T. Premature senescence of mesothelial cells is associated with non-telomeric DNA damage. Biochemical and Biophysical Research Communications 2007, 362(3), 707-711.
- Richter T, Saretzki G, Nelson G, Melcher M, Olijslagers S, von Zglinicki T. TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts. Mechanisms of Ageing and Development 2007, 128(4), 340-345.
- Passos JF, Von Zglinicki T, Saretzki G. Mitochondrial dysfunction and cell senescence: Cause or consequence?. In: 2nd Conference on Strategies for Engineered Negligible Senescence (SENS). 2006, Cambridge: Rejuvenation Research, Mary Ann Liebert, Inc. Publishers.
- Jeyapalan J, Saretzki G, Leake A, Tilby MJ, VonZglinicki TW. Neuroblastoma cell apoptosis induction after cisplatin treatment is not telomere–dependent. International Journal of Cancer 2006, 118(11), 2727-34.
- Jeyapalan, J., Saretzki, G., Leake, A., Tilby, M.J., Von Zglinicki, T. Tumour-cell apoptosis after cisplatin treatment is not telomere dependent. International Journal of Cancer 2006, 118(11), 2727-2734.
- Michailidis G, Saretzki G, Hall J. Endogenous and ectopic expression of telomere regulating genes in chicken embryonic fibroblasts. Biochemical and Biophysical Research Communications 2005, 335(1), 240-246.
- von Zglinicki T, Saretzki G, Ladhoff J, di Fagagna FD, Jackson SP. Human cell senescence as a DNA damage response. In: Mechanisms of Ageing and Development: 2nd International Conference on Functional Genomics of Ageing. 2005, Hersonissos, Greece: Elsevier Ireland Ltd.
- Armstrong L, Saretzki G, Peters H, Wappler I, Evans J, Hole N, Von Zglinicki T, Lako M. Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage. Stem Cells 2005, 23(4), 516-529.
- Von Zglinicki T, Martin-Ruiz CM, Saretzki G. Telomeres, cell senescence and human ageing. Signal Transduction 2005, 5(3), 103-114.
- Saretzki GC. Telomeres, senescence and longevity: The role of oxidative stress and antioxidants. Current Pharmacogenomics 2005, 3(2), 129-156.
- Lechel A, Satyanarayana A, Ju Z, Plentz RR, Schaetzlein S, Rudolph C, Wilkens L, Wiemann SU, Saretzki G, Malek NP, Manns MP, Buer J, Rudolph KL. The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo. EMBO Reports 2005, 6(3), 275-281.
- Armstrong L, Lako M, van Herpe I, Evans J, Saretzki G, Hole N. A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation. Mechanisms of Development 2004, 121(12), 1509-1522.
- Martin-Ruiz C, Saretzki G, Petrie J, Ladhoff J, Jeyapalan J, Wei W, Sedivy J, Von Zglinicki T. Stochastic Variation in Telomere Shortening Rate Causes Heterogeneity of Human Fibroblast Replicative Life Span. Journal of Biological Chemistry 2004, 279(17), 17826-17833.
- Saretzki G, Armstrong L, Leake A, Lako M, Von Zglinicki T. Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cells. Stem Cells 2004, 22(6), 962-971.
- Keys B, Serra V, Saretzki G, von Zglinicki T. Telomere shortening in human fibroblasts is not dependent on the size of the telomeric-3′-overhang. Aging Cell 2004, 3(3), 103-109.
- Jeyapalan, J., Leake, A., Ahmed, S., Saretzki, G., Tilby, M.J., Von Zglinicki, T. The role of telomeres in etoposide induced tumor cell death. Cell Cycle 2004, 3(9), 1169-1176.
- D'Adda Di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003, 426(6963), 194-198.
- Saretzki G, Serra V, Lorenz M, von Zglinicki T. Extracellular superoxide dismutase is a major antioxidant and slows down telomere shortening in human fibroblasts. In: Free Radical Research: Meeting on Free Radicals and Oxidative Stress. 2003, Ioannina, Greece: Informa Healthcare.
- Serra V, Von Zglinicki T, Lorenz M, Saretzki G. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. Journal of Biological Chemistry 2003, 278(9), 6824-6830.
- Davies, B.R., Steele, I.A., Edmondson, R.J., Zwolinski, S.A., Saretzki, G., Von Zglinicki, T., O'Hare, M.J. Immortalisation of human ovarian surface epithelium with telomerase and temperature-senstitive SV40 large T antigen. Experimental Cell Research 2003, 288(2), 390-402.
- Saretzki G, Murphy MP, von Zglinicki T. MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell 2003, 2(2), 141-143.
- Saretzki G, Von Zglinicki T. Telomerase as a promising target for human cancer gene therapy. Drugs of Today 2003, 39(4), 265-276.
- Saretzki G. Telomerase inhibition as cancer therapy. Cancer Letters 2003, 194(2), 209-219.
- Saretzki G, Petersen S, Petersen I, Kolble K, Von Zglinicki T. hTERT gene dosage correlates with telomerase activity in human lung cancer cell lines. Cancer Letters 2002, 176(1), 81-91.
- Saretzki G, Von Zglinicki T. Replicative aging, telomeres, and oxidative stress. Annals of the New York Academy of Sciences 2002, 959(1), 24-29.
- Saretzki G, Von Zglinicki T. Replicative aging, telomeres, and oxidative stress. In: Increasing Healthy Life Span: Conventional Measures and Slowing the Innate Aging Process. 2002, Vancouver, British Colombia, Canada: New York Academy of Sciences.
- Lorenz M, Saretzki G, Sitte N, Metzkow S, Von Zglinicki T. BJ fibroblasts display high antioxidant capacity and slow telomere shortening independent of hTERT transfection. Free Radical Biology and Medicine 2001, 31(6), 824-831.
- Ludwig A, Saretzki G, Holm PS, Tiemann F, Lorenz M, Emrich T, Harley CB, von Zglinicki T. Ribozyme cleavage of telomerase mRNA sensitizes breast epithelial cells to inhibitors of topoisomerase. Cancer Research 2001, 61(7), 3053-3061.
- Saretzki G, Ludwig A, Von Zglinicki T, Runnebaum IB. Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells. Cancer Gene Therapy 2001, 8(10), 827-834.
- Saretzki G, Fischer H, Kaufmann IG, Schewe C, Nadjari B, Blohmer J, Hauptmann S. Telomerase activity in cervical smears. Analytical Cellular Pathology 2001, 23(1), 39-43.
- von Zglinicki T, Serra V, Lorenz M, Saretzki G, Lenzen-Grossimlighaus R, Gessner R, Risch A, Steinhagen-Thiessen E. Short telomeres in patients with vascular dementia: An indicator of low antioxidative capacity and a possible risk factor?. Laboratory Investigation 2000, 80(11), 1739-1747.
- Serra V, Grune T, Sitte N, Saretzki G, Von Zglinicki T. Telomere length as a marker of oxidative stress in primary human fibroblast cultures. Annals of the New York Academy of Sciences 2000, 908, 327-330.
- Saretzki G, von Zglinicki T. [Replicative senescence as a model of aging: the role of oxidative stress and telomere shortening--an overview]. Zeitschrift fur Gerontologie und Geriatrie 1999, 32(2), 69-75.
- Pilger R, Sitte N, Saretzki G, von Zglinicki T. Modification of the replicative life-span of human fibroblasts by oxidative stress. Zeitschrift Fur Gerontologie Und Geriatrie 1999, 32, 887.
- von Zglinicki T, Ludwig A, Saretzki G. Ribozymes inhibiting the catalytic subunit of human telomerase (hTERT). Germany & International, DE199039615, INT10003356, 1999.
- Saretzki G, Sitte N, Merkel U, Wurm RE, von Zglinicki T. Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments. Oncogene 1999, 18(37), 5148-5158.
- Sitte N, Saretzki G, von Zglinicki T. Accelerated telomere shortening in flbroblasts after extended periods of confluency. Free Radical Biology and Medicine 1998, 24, 885-893.
- Mueller JD, Haegle N, Keller G, Mueller E, Saretzky G, Bethke B, Stolte M, Hofler H. Loss of heterozygosity and microsatellite instability in de novo versus ex-adenoma carcinomas of the colorectum. Am J Pathol 1998, 153(6), 1977-84.
- Petersen S, Saretzki G, von Zglinicki T. Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Experimental Cell Research 1998, 239(1), 152-160.
- Saretzki G, Feng JL, von Zglinicki T, Villeponteau B. Similar gene expression pattern in senescent and hyperoxic- treated fibroblasts. Journals of Gerontology Series a-Biological Sciences and Medical Sciences 1998, 53, B438-B442.
- Saretzki G, Hoffmann U, Rohlke P, Psille R, Gaigal T, Keller G, Hofler H, Loning T, Petersen I, Dietel M. Identification of allelic losses in benign, borderline, and invasive epithelial ovarian tumors and correlation with clinical outcome. Cancer 1997, 80, 1241-1249.
- Reichmuth C, Markus MA, Hillemanns M, Atkinson MJ, Unni KK, Saretzki G, Hofler H. The diagnostic potential of the chromosome translocation t(2;13) in rhabdomyosarcoma: a Pcr study of fresh-frozen and paraffin-embedded tumour samples. Journal of Pathology 1996, 180, 50-7.
- von Zglinicki T, Saretzki G, Docke W, Lotze C. Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence?. Experimental Cell Research 1995, 220, 186-193.