cell aging

Summary

Summary: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.

Top Publications

  1. ncbi Cellular senescence: when bad things happen to good cells
    Judith Campisi
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA
    Nat Rev Mol Cell Biol 8:729-40. 2007
  2. ncbi Oxidants, oxidative stress and the biology of ageing
    T Finkel
    Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
    Nature 408:239-47. 2000
  3. pmc The essence of senescence
    Thomas Kuilman
    Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Genes Dev 24:2463-79. 2010
  4. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
  5. ncbi 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
  6. ncbi Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
    Wen Xue
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nature 445:656-60. 2007
  7. pmc Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
    Zhenbang Chen
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    Nature 436:725-30. 2005
  8. pmc Four faces of cellular senescence
    Francis Rodier
    The Research Centre of the University of Montreal Hospital Centre Institut du Cancer de Montréal, Montreal, Quebec, Canada
    J Cell Biol 192:547-56. 2011
  9. pmc Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
    Darren J Baker
    Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Nature 479:232-6. 2011
  10. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006

Detail Information

Publications349 found, 100 shown here

  1. ncbi Cellular senescence: when bad things happen to good cells
    Judith Campisi
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA
    Nat Rev Mol Cell Biol 8:729-40. 2007
    ....
  2. ncbi Oxidants, oxidative stress and the biology of ageing
    T Finkel
    Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
    Nature 408:239-47. 2000
    ..Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span...
  3. pmc The essence of senescence
    Thomas Kuilman
    Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Genes Dev 24:2463-79. 2010
    ..Additionally, we highlight the power and limitations of the biomarkers currently used to identify senescent cells in vitro and in vivo...
  4. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
    ..Negation of ras-induced senescence may be relevant during multistep tumorigenesis...
  5. ncbi 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...
  6. ncbi Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
    Wen Xue
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nature 445:656-60. 2007
    ..Our study indicates that p53 loss can be required for the maintenance of aggressive carcinomas, and illustrates how the cellular senescence program can act together with the innate immune system to potently limit tumour growth...
  7. pmc Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
    Zhenbang Chen
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    Nature 436:725-30. 2005
    ..Our results demonstrate the relevance of cellular senescence in restricting tumorigenesis in vivo and support a model for cooperative tumour suppression in which p53 is an essential failsafe protein of Pten-deficient tumours...
  8. pmc Four faces of cellular senescence
    Francis Rodier
    The Research Centre of the University of Montreal Hospital Centre Institut du Cancer de Montréal, Montreal, Quebec, Canada
    J Cell Biol 192:547-56. 2011
    ..The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks...
  9. pmc Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
    Darren J Baker
    Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Nature 479:232-6. 2011
    ..These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan...
  10. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006
    ..Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication...
  11. ncbi Oxidative stress shortens telomeres
    Thomas von Zglinicki
    Dept Gerontology, University of Newcastle, Wolfson Research Centre, General Hospital, Newcastle upon Tyne, UK
    Trends Biochem Sci 27:339-44. 2002
    ..This might have evolved to block the growth of cells that have been exposed to a high risk of mutation...
  12. pmc Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor
    Jean Philippe Coppe
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    PLoS Biol 6:2853-68. 2008
    ..Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment...
  13. ncbi Extension of life-span by introduction of telomerase into normal human cells
    A G Bodnar
    Geron Corporation, Menlo Park, CA 94025, USA
    Science 279:349-52. 1998
    ..The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine...
  14. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
    ..Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression...
  15. pmc DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence
    Olga V Leontieva
    Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3 312, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Aging (Albany NY) 2:924-35. 2010
    ..We conclude that induction of p53 does not activate the senescence program in quiescent cells. In cells with induced p53, re-activation of mTOR by serum stimulation causes senescence, as an equivalent of cellular growth...
  16. ncbi Restoration of p53 function leads to tumour regression in vivo
    Andrea Ventura
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nature 445:661-5. 2007
    ..These results support efforts to treat human cancers by way of pharmacological reactivation of p53...
  17. ncbi Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
    Masashi Narita
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Cell 113:703-16. 2003
    ..These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor...
  18. pmc Accelerated telomere shortening in response to life stress
    Elissa S Epel
    Department of Psychiatry, University of California, 3333 California Street, Suite 465, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 101:17312-5. 2004
    ..These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases...
  19. ncbi Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo
    Florence Debacq-Chainiaux
    Department of Biology, Faculty of Sciences, Research Unit on Cellular Biology URBC, University of Namur FUNDP, Namur, Belgium
    Nat Protoc 4:1798-806. 2009
    ..The cytochemical method is applicable to tissue sections and requires simple reagents and equipment. The fluorescence-based methods have the advantages of being more quantitative and sensitive...
  20. pmc Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
    Francis Rodier
    Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Nat Cell Biol 11:973-9. 2009
    ..Thus, in addition to orchestrating cell-cycle checkpoints and DNA repair, a new and important role of the DDR is to allow damaged cells to communicate their compromised state to the surrounding tissue...
  21. pmc Senescence in tumours: evidence from mice and humans
    Manuel Collado
    Spanish National Cancer Research Centre, Madrid, Spain
    Nat Rev Cancer 10:51-7. 2010
    ..Standard chemotherapy also has the potential to induce senescence, which may partly underlie its therapeutic activity. Although these concepts are well supported in mouse models, translating them to clinical oncology remains a challenge...
  22. ncbi Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
    Judith Campisi
    Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Cell 120:513-22. 2005
    ..Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate...
  23. ncbi BRAFE600-associated senescence-like cell cycle arrest of human naevi
    Chrysiis Michaloglou
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 436:720-4. 2005
    ..Thus, both in vitro and in vivo, BRAF(V600E)-expressing melanocytes display classical hallmarks of senescence, suggesting that oncogene-induced senescence represents a genuine protective physiological process...
  24. pmc Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 4:159-65. 2012
    ....
  25. ncbi Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a)
    Utz Herbig
    Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA
    Mol Cell 14:501-13. 2004
    ..Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals...
  26. ncbi AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
    Russell G Jones
    Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 18:283-93. 2005
    ..However, persistent activation of AMPK leads to accelerated p53-dependent cellular senescence. Thus, AMPK is a cell-intrinsic regulator of the cell cycle that coordinates cellular proliferation with carbon source availability...
  27. pmc Hypoxia suppresses conversion from proliferative arrest to cellular senescence
    Olga V Leontieva
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Proc Natl Acad Sci U S A 109:13314-8. 2012
    ..Thus, in normal and cancer cell lines, hypoxia suppresses geroconversion caused by diverse stimuli. Physiological and clinical implications of the present findings are discussed...
  28. pmc Feedback between p21 and reactive oxygen production is necessary for cell senescence
    João 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...
  29. pmc The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway
    Lioubov G Korotchkina
    Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3 312, Buffalo, NY 14263, USA
    Aging (Albany NY) 2:344-52. 2010
    ..We conclude that status of the mTOR pathway can determine, at least in part, the choice between senescence and quiescence in p53-arrested cells...
  30. ncbi Vitamin C enhances the generation of mouse and human induced pluripotent stem cells
    Miguel Angel Esteban
    Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China
    Cell Stem Cell 6:71-9. 2010
    ..Our results therefore highlight a straightforward method for improving the speed and efficiency of iPSC generation and provide additional insights into the mechanistic basis of the reprogramming process...
  31. ncbi Oncogene-induced senescence as an initial barrier in lymphoma development
    Melanie Braig
    Charité Universitätsmedizin Berlin Haematology Oncology, 13353 Berlin, Germany
    Nature 436:660-5. 2005
    ..These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras...
  32. pmc Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells
    Hiroshi Tazawa
    Biochemistry Division, National Cancer Center Research Institute, 5 1 1 Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    Proc Natl Acad Sci U S A 104:15472-7. 2007
    ..Abrogation of miR-34a function could contribute to aberrant cell proliferation, leading to colon cancer development...
  33. ncbi Rejuvenation of aged progenitor cells by exposure to a young systemic environment
    Irina M Conboy
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 433:760-4. 2005
    ..These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age...
  34. ncbi Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
    Tae Won Kang
    Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany
    Nature 479:547-51. 2011
    ....
  35. pmc Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells
    Olga V Leontieva
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 11:4642-9. 2012
    ..We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence...
  36. ncbi Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans)
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:683-8. 2010
    ..Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?..
  37. ncbi Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
    Andrew S Brack
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
    Science 317:807-10. 2007
    ..These results indicate that the Wnt signaling pathway may play a critical role in tissue-specific stem cell aging and an increase in tissue fibrosis with age.
  38. pmc The senescence-associated secretory phenotype: the dark side of tumor suppression
    Jean Philippe Coppe
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Annu Rev Pathol 5:99-118. 2010
    ..The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression...
  39. pmc Reversal of human cellular senescence: roles of the p53 and p16 pathways
    Christian M Beausejour
    Lawrence Berkeley National Laboratory, MS 84 171, 1 Cyclotron Road, Berkeley, CA 94720, USA
    EMBO J 22:4212-22. 2003
    ..Our results indicate that the senescence response to telomere dysfunction is reversible and is maintained primarily by p53. However, p16 provides a dominant second barrier to the unlimited growth of human cells...
  40. pmc Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis
    Veronique Nogueira
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
    Cancer Cell 14:458-70. 2008
    ..Given that rapamycin alone is mainly cytostatic, this constitutes a strategy for cancer therapy that selectively eradicates cancer cells via Akt activation...
  41. ncbi Tumour biology: senescence in premalignant tumours
    Manuel Collado
    Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Nature 436:642. 2005
    ..Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer...
  42. pmc p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype
    Adam Freund
    Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    EMBO J 30:1536-48. 2011
    ..These findings assign p38MAPK a novel role in SASP regulation--one that is necessary, sufficient, and independent of previously described pathways...
  43. ncbi Living on a break: cellular senescence as a DNA-damage response
    Fabrizio d'Adda di Fagagna
    IFOM Foundation, FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Cancer 8:512-22. 2008
    ....
  44. ncbi Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
    Keisuke Ito
    Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Nat Med 12:446-51. 2006
    ..These data show that inactivation of p38 MAPK protects HSCs against loss of self-renewal capacity. Our characterization of molecular mechanisms that limit HSC lifespan may lead to beneficial therapies for human disease...
  45. ncbi AtNAP, a NAC family transcription factor, has an important role in leaf senescence
    Yongfeng Guo
    Department of Horticulture, 119 Plant Science, Cornell University, Ithaca, NY 14853 5904, USA
    Plant J 46:601-12. 2006
    ..Furthermore, inducible overexpression of AtNAP causes precocious senescence. These data strongly suggest that AtNAP and its homologs play an important role in leaf senescence in Arabidopsis and possibly in other plant species...
  46. pmc Inflammatory networks during cellular senescence: causes and consequences
    Adam Freund
    Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Trends Mol Med 16:238-46. 2010
    ..We also summarize the cellular pathways/processes that are known to regulate this phenotype--namely, the DNA damage response, microRNAs, key transcription factors and kinases and chromatin remodeling...
  47. ncbi Cellular senescence in cancer and aging
    Manuel Collado
    Spanish National Cancer Research Center CNIO, Madrid, Spain
    Cell 130:223-33. 2007
    ..Together these mechanisms limit excessive or aberrant cellular proliferation, and so the state of senescence protects against the development of cancer. Recent evidence suggests that cellular senescence also may be involved in aging...
  48. pmc Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging
    A Krtolica
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 98:12072-7. 2001
    ..Our findings suggest that, although cellular senescence suppresses tumorigenesis early in life, it may promote cancer in aged organisms, suggesting it is an example of evolutionary antagonistic pleiotropy...
  49. ncbi DNA damage response and cellular senescence in tissues of aging mice
    Chunfang Wang
    Ageing Research Laboratories, Institute for Ageing and Health and Center for Integrated Systems Biology of Ageing and Nutrition CISBAN, Newcastle University, Newcastle upon Tyne NE4 6BE, UK
    Aging Cell 8:311-23. 2009
    ..X foci and telomeres even in crypts from very old mice, indicating that senescence in the crypt enterocytes is telomere independent. The results suggest that stress-dependent cell senescence could play a causal role for aging of mice...
  50. pmc SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
    Eriko Michishita
    Department of Medicine, Division of Endocrinology, Gerontology and Metabolism, School of Medicine, Stanford University, Stanford, California 94305, USA
    Nature 452:492-6. 2008
    ..Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome...
  51. pmc The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence
    Karl Agger
    Biotech Research and Innovation Centre BRIC and Centre for Epigenetics, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Genes Dev 23:1171-6. 2009
    ..Additionally, inhibition of Jmjd3 expression in mouse embryonic fibroblasts results in suppression of p16Ink4a and p19Arf expression and in their immortalization...
  52. pmc Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation
    Tamir Chandra
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Mol Cell 47:203-14. 2012
    ..These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events...
  53. pmc Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression
    Olga V Leontieva
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 3:1078-91. 2011
    ..We discuss that although CS does not mimic organismal aging, the same signal transduction pathways that drive CS also drive aging...
  54. pmc Cell cycle arrest is not senescence
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 3:94-101. 2011
    ..Also, the relation between cancer and senescence is distorted. Here I discuss why the link between arrest and senescence is semi-coincidental and how senescence is related to aging and cancer...
  55. ncbi Tumor cell senescence in cancer treatment
    Igor B Roninson
    Department of Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607 7170, USA
    Cancer Res 63:2705-15. 2003
    ....
  56. pmc Replicative senescence of mesenchymal stem cells: a continuous and organized process
    Wolfgang Wagner
    Department of Medicine V, University of Heidelberg, Heidelberg, Germany
    PLoS ONE 3:e2213. 2008
    ..This process includes far reaching alterations in phenotype, differentiation potential, global gene expression patterns, and miRNA profiles that need to be considered for therapeutic application of MSC preparations...
  57. pmc Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity
    Yuchen Chien
    Cold Spring Harbor Laboratory, New York 11724, USA
    Genes Dev 25:2125-36. 2011
    ..Our results demonstrate that NF-κB controls both cell-autonomous and non-cell-autonomous aspects of the senescence program and identify a tumor-suppressive function of NF-κB that contributes to the outcome of cancer therapy...
  58. pmc mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis
    Ramiro Iglesias-Bartolomé
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20852, USA
    Cell Stem Cell 11:401-14. 2012
    ..mTOR inhibition also protects from the loss of proliferative basal epithelial stem cells upon ionizing radiation in vivo, thereby preserving the integrity of the oral mucosa and protecting from radiation-induced mucositis...
  59. pmc Paradoxical suppression of cellular senescence by p53
    Zoya N Demidenko
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Proc Natl Acad Sci U S A 107:9660-4. 2010
    ..Thus, in spite of its ability to induce cell cycle arrest, p53 can act as a suppressor of cellular senescence...
  60. pmc Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence
    Marina Kolesnichenko
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    Cell Cycle 11:2391-401. 2012
    ..These results indicate that TORC1 is an integral component of the signaling pathway that mediates cellular senescence...
  61. ncbi Vascular cell senescence: contribution to atherosclerosis
    Tohru Minamino
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1 8 1 Inohana, Chuo Ku, Chiba 260 8670, Japan
    Circ Res 100:15-26. 2007
    ..In this review, we examine the hypothesis that cellular senescence might contribute to atherosclerosis, which is a characteristic of aging in humans...
  62. pmc Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence
    Roderik M Kortlever
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 1211066 CX Amsterdam, The Netherlands
    Nat Cell Biol 8:877-84. 2006
    ..Our data indicate that PAI-1 is not merely a marker of senescence, but is both necessary and sufficient for the induction of replicative senescence downstream of p53...
  63. ncbi DNA damage is able to induce senescence in tumor cells in vitro and in vivo
    Robert H te Poele
    Department of Medical Oncology, St Bartholomew s Hospital, London
    Cancer Res 62:1876-83. 2002
    ..Thus, like apoptosis, senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome...
  64. pmc Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS
    Marta Barradas
    Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College, London W12 0NN, United Kingdom
    Genes Dev 23:1177-82. 2009
    ..Our findings directly implicate JMJD3 in the regulation of INK4a/ARF during oncogene-induced senescence and suggest that JMJD3 has the capacity to act as a tumor suppressor...
  65. ncbi Cellular senescence as a tumor-suppressor mechanism
    J Campisi
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Trends Cell Biol 11:S27-31. 2001
    ..Recent findings have revealed the complexities of the senescence phenotype and unexpected possible consequences for the organism...
  66. pmc Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
    Hui Kuan Lin
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 464:374-9. 2010
    ..Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy...
  67. ncbi p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC
    N R Christoffersen
    Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
    Cell Death Differ 17:236-45. 2010
    ..Hence, in addition to its integration in the p53 pathway, we show that alternative cancer-related pathways regulate miR-34a, emphasising its significance as a tumour suppressor...
  68. 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
    ....
  69. ncbi Rapamycin decelerates cellular senescence
    Zoya N Demidenko
    Oncotarget, Albany, NY, USA
    Cell Cycle 8:1888-95. 2009
    ..During cell cycle arrest, rapamycin transformed the irreversible arrest into a reversible condition. Our data demonstrate that senescence can be pharmacologically suppressed...
  70. ncbi Cellular senescence in aging primates
    Utz Herbig
    Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, USA
    Science 311:1257. 2006
    ..In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status...
  71. pmc Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression
    Colleen A Brady
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 145:571-83. 2011
    ....
  72. ncbi Leaf senescence
    Pyung Ok Lim
    Department of Science Education, Cheju National University Jeju, Jeju 690 756, Korea
    Annu Rev Plant Biol 58:115-36. 2007
    ....
  73. pmc TAp63 induces senescence and suppresses tumorigenesis in vivo
    Xuecui Guo
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Nat Cell Biol 11:1451-7. 2009
    ..The ability of TAp63 to trigger senescence and halt tumorigenesis irrespective of p53 status identifies TAp63 as a potential target of anti-cancer therapy for human malignancies with compromised p53...
  74. ncbi Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells
    Karin Stenderup
    University Department of Endocrinology and Metabolism, University Hospital of Aarhus, DK 8000 Aarhus C, Denmark
    Bone 33:919-26. 2003
    ..In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation...
  75. ncbi Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies
    A Stolzing
    Kroto Research Institute, North Campus, University of Sheffield, UK
    Mech Ageing Dev 129:163-73. 2008
    ..Furthermore, there is an age-related decline in overall BM MSC "fitness" which might lead to problems when using autologous aged MSC for cell-based therapies...
  76. ncbi Suppression of replicative senescence by rapamycin in rodent embryonic cells
    Tatiana V Pospelova
    Institute of Cytology, St Petersburg, Russia
    Cell Cycle 11:2402-7. 2012
    ..Following rapamycin treatment and removal, a fraction of proliferating REFs gradually increased and senescent phenotype disappeared completely by passage 24...
  77. ncbi Pro-senescence therapy for cancer treatment
    Caterina Nardella
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA
    Nat Rev Cancer 11:503-11. 2011
    ..In this Opinion article, we focus on concepts that are relevant to a pro-senescence approach to therapy and we propose potential therapeutic strategies that aim to enhance the pro-senescence response in tumours...
  78. ncbi Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition
    Mikhail V Blagosklonny
    Cell Cycle 5:2087-102. 2006
    ..Finally, I discuss that extended life span will reveal new causes for aging (e.g., ROS, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first...
  79. pmc Accumulation of senescent cells in mitotic tissue of aging primates
    Jessie C Jeyapalan
    Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA
    Mech Ageing Dev 128:36-44. 2007
    ..The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event...
  80. pmc miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues
    Laura R Saunders
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, 94158, USA
    Aging (Albany NY) 2:415-31. 2010
    ..The regulation of SIRT1 protein levels by miRNAs might provide new opportunities for therapeutic tissue-specific modulation of SIRT1 expression and for reprogramming of somatic cells into iPS cells...
  81. ncbi Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence
    Carmen Guerra
    Experimental Oncology, Centro Nacional de Investigaciones Oncologicas CNIO, Madrid, Spain
    Cancer Cell 19:728-39. 2011
    ..These results support the concept that antiinflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC...
  82. pmc Five dysfunctional telomeres predict onset of senescence in human cells
    Zeenia Kaul
    Cancer Research Unit, Children s Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia
    EMBO Rep 13:52-9. 2012
    ....
  83. ncbi Quantitative assessment of markers for cell senescence
    Conor Lawless
    Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Exp Gerontol 45:772-8. 2010
    ..The technique presented is a framework for quantitative assessment of markers for senescence...
  84. ncbi Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
    Christopher J Sarkisian
    Department of Cancer Biology, The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
    Nat Cell Biol 9:493-505. 2007
    ..We suggest a three-stage model for Ras-induced tumorigenesis consisting of an initial activating Ras mutation, overexpression of the activated Ras allele and, finally, evasion of p53-Ink4a-Arf-dependent senescence checkpoints...
  85. pmc How to track cellular aging of mesenchymal stromal cells?
    Wolfgang Wagner
    Helmholtz Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany
    Aging (Albany NY) 2:224-30. 2010
    ..Molecular analysis of a suitable panel of genes might provide a robust tool to assess efficiency and safety of long-term expansion...
  86. ncbi Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
    Konrad T Howitz
    BIOMOL Research Laboratories, Inc, 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
    Nature 425:191-6. 2003
    ..We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators...
  87. pmc DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion
    Francis Rodier
    Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
    J Cell Sci 124:68-81. 2011
    ..Thus, DNA-SCARS are dynamically formed distinct structures that functionally regulate multiple aspects of the senescent phenotype...
  88. pmc mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging
    Rogerio M Castilho
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Stem Cell 5:279-89. 2009
    ....
  89. pmc Phosphorylation of HuR by Chk2 regulates SIRT1 expression
    Kotb Abdelmohsen
    Laboratory of Cellular and Molecular Biology, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Cell 25:543-57. 2007
    ..Our findings demonstrate that HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes...
  90. ncbi Weak p53 permits senescence during cell cycle arrest
    Olga V Leontieva
    Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:4323-7. 2010
    ..We conclude that low p53 levels during prolonged cell cycle arrest tend to cause senescence, whereas high levels of p53 tend to cause either quiescence or cell death...
  91. ncbi Pharmacologic inhibition of MEK and PI-3K converges on the mTOR/S6 pathway to decelerate cellular senescence
    Zoya N Demidenko
    Oncotarget, Albany, NY, USA
    Cell Cycle 8:1896-900. 2009
    ..Taken together this suggests that (a) simultaneous activation of PI-3K and MEK is required to ensure cellular senescence and (b) U0126 and LY294002 suppress senescence via the rapamycin-sensitive pathway...
  92. ncbi Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence
    Stéphane Ansieau
    INSERM, U590, Lyon F 69008, France
    Cancer Cell 14:79-89. 2008
    ..These findings suggest an unanticipated direct link between early escape from failsafe programs and the acquisition of invasive features by cancer cells...
  93. pmc Telomeres and telomerase in cancer
    Steven E Artandi
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Carcinogenesis 31:9-18. 2010
    ..This review covers the role of telomeres and telomerase in the biology of normal tissue stem/progenitor cells and in the development of cancer...
  94. pmc Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence
    Emma Langley
    Wellcome Institute Cancer Research UK and Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QR, UK
    EMBO J 21:2383-96. 2002
    ..Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence...
  95. pmc Aging and replicative senescence have related effects on human stem and progenitor cells
    Wolfgang Wagner
    Department of Medicine V, University of Heidelberg, Heidelberg, Germany
    PLoS ONE 4:e5846. 2009
    ..Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo...
  96. ncbi How to make a melanoma: what do we know of the primary clonal events?
    Dorothy C Bennett
    Division of Basic Medical Sciences, St George s, University of London, London, UK
    Pigment Cell Melanoma Res 21:27-38. 2008
    ..The data support a model in which genesis of melanoma requires changes that (1) initiate clonal expansion, (2) overcome cell senescence, and (3) reduce apoptosis...
  97. pmc DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells
    Simone Bork
    Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany
    Aging Cell 9:54-63. 2010
    ..This supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications...
  98. ncbi Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay
    Koji Itahana
    Department of Radiation Oncology, School of Medicine, The University of North Carolina, Chapel Hill, NC, USA
    Methods Mol Biol 371:21-31. 2007
    ..Because it is easy to detect, SA-beta-gal is currently a widely used biomarker of senescence. Here we describe a method to detect SA-beta-gal in detail, including some recent modifications...
  99. ncbi MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1
    Rossella Menghini
    Department of Internal Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    Circulation 120:1524-32. 2009
    ..miR-217 regulates the expression of silent information regulator 1 (SirT1), a major regulator of longevity and metabolic disorders that is progressively reduced in multiple tissues during aging...
  100. ncbi At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence
    Zoya N Demidenko
    Oncotarget, Albany, NY, USA
    Cell Cycle 8:1901-4. 2009
    ....
  101. ncbi Pseudo-DNA damage response in senescent cells
    Tatyana V Pospelova
    Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia
    Cell Cycle 8:4112-8. 2009
    ..Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells...

Research Grants69

  1. Weight Loss &Exercise Effects on Telomere Length in Postmenopausal Women
    ANNE M MCTIERNAN; Fiscal Year: 2012
    ..Shorter telomeres have been linked to cancer risk. The project includes 438 postmenopausal, overweight/obese, sedentary women who have already completed the trial from which blood samples will be used. ..
  2. OLIGOCLONAL T CELL EXPANSION AND RHEUMATOID ARTHRITIS
    Cornelia M Weyand; Fiscal Year: 2012
    ..functions, revealed a defect in T cell generation that imposes proliferative stress and causes accelerated T cell aging. The current application will investigate this defect in T cell homeostasis and builds on our preliminary data, ..
  3. Hematopoietic Stem Cells (HSCs) as Juvenile Protective Factors that Alter Aging
    David E Harrison; Fiscal Year: 2011
    ..Understanding the factors and mechanisms of stem cell aging will help identify phenotypes in juveniles that predict functional defects in old age...
  4. Role of Matrix Metalloproteinase-1 in Endothelial Cell Senescence
    Catherine D Mao; Fiscal Year: 2010
    ....
  5. Telomere and its bio-regulators as predictors for clinical diabetes in women
    Simin Liu; Fiscal Year: 2010
    ..contributes to senescence and apoptosis, indicating that telomere length can be used as a critical biomarker for cell aging. It is now increasingly recognized that telomere attrition also contributes to the pathogenesis of several age-..
  6. RISK FACTORS FOR CVD IN WOMEN
    JOANN ELISABETH MANSON; Fiscal Year: 2012
    ..These promising biochemical and genetic markers may have implications for improving prevention strategies, enhancing treatment options, and generating additional testable hypotheses for heart disease research. ..
  7. Chronic Toll-like Receptor Ligation and Hematopoietic Stem Cell Aging
    Brandt L Esplin; Fiscal Year: 2010
    ..This information may lead to clinical applications that prolong life in aged or immune-compromised patients by preserving the integrity of the immune system during challenging circumstances. ..
  8. Role of endocrine-disrupting chemicals and social stress on perinatal outcomes
    Ami R Zota; Fiscal Year: 2012
    ..Results from this work will improve pregnancy outcomes and inform public health policy, particularly for vulnerable subpopulations, who often encounter elevated exposures to chemical and non-chemical stressors. ..
  9. Molecular Mechanisms of Age-related Impairment of Muscle Regeneration
    Thomas A Rando; Fiscal Year: 2013
    ..mutants and pharmacological approaches to determine to what extent the Wnt-mediated effects of muscle stem cell aging are related to each of these pathways that play important roles in determining organismal aging...
  10. BIOLOGICAL PROPERTIES OF RPE MELANIN
    Janice M Burke; Fiscal Year: 2010
    ..The effects of age on melanosomes will also be studied to determine whether their ability to protect RPE cells from stress declines over time, which could contribute to diseases of the retina such as age-related macular degeneration. ..
  11. Human tendon stem progenitor cell aging and regeneration
    Hui Bin Sun; Fiscal Year: 2013
    ..These findings may provide new insights into the basis for age-related tendon disorders, and the development of new strategies for tendon repair and regeneration. ..
  12. 2011 Cold Spring Harbor Conference on Telomeres and Telomerase
    David J Stewart; Fiscal Year: 2010
    ..The 2011 meeting will result in vigorous discussion and synergistic interactions stimulated by the presentation of a large body of unpublished data. ..
  13. Effects of exercise and life stress on telomere maintenance and CVD risk
    Eli Puterman; Fiscal Year: 2013
    ..complete successful apprenticeships with leading experts in cardiovascular disease, exercise interventions, and cell aging. The proposed training will include brief courses offered through UCSF, UC Berkeley, NIH, CDC, and Johns Hopkins...
  14. Effects of exercise and life stress on telomere maintenance and CVD risk
    Eli Puterman; Fiscal Year: 2012
    ..complete successful apprenticeships with leading experts in cardiovascular disease, exercise interventions, and cell aging. The proposed training will include brief courses offered through UCSF, UC Berkeley, NIH, CDC, and Johns Hopkins...
  15. Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
    Michael D Stone; Fiscal Year: 2013
    ..a progressive shortening of telomere length with each round of cell division provides a molecular signal for cell aging and regulates entry into permanent cell growth arrest...
  16. Cardiac Stem Cells and Diabetic Cardiomyopathy
    Jan Kajstura; Fiscal Year: 2010
    ..Most importantly, we may be able to identify a genetic link between diabetes and ROS, on the one hand, and premature cellular senescence and heart failure, on the other. ..
  17. Chronic and Acute Psychosocial Stress and Impaired Cell Aging
    Elissa S Epel; Fiscal Year: 2013
    ..We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo...
  18. Stress, Cellular Aging and Susceptibility to Infectious Disease
    Sheldon A Cohen; Fiscal Year: 2010
    ..An in-depth understanding of the role how stress influences our health can help lead to effective interventions to protect people at risk. ..
  19. HPV &Cervix Neoplasia in a Large, Long Term HIV + Cohort
    Howard D Strickler; Fiscal Year: 2013
    ..High CD8+ activation may cause accelerated T-cell aging / differentiation, and is reported to increase the number of terminally differentiated T-cells with diminished ..
  20. Cellular and molecular mechanisms of aging and regeneration in colonial chordate
    Irving L Weissman; Fiscal Year: 2013
    ..In this colonial model organism, we can clearly define that stem cell aging is the root cause of senescence of the entire colony...
  21. Role of endocrine-disrupting chemicals and social stress on perinatal outcomes
    Ami R Zota; Fiscal Year: 2013
    ..abstract_text> ..
  22. The functions and mechanism of SHSP degradation in Escherichia coli
    ELLEN FRANCES VIEUX; Fiscal Year: 2011
    ....
  23. Stress, Mood, Omega-3 Fatty Acids, &Telomeric Aging: Randomized Controlled Trial
    Janice K Kiecolt-Glaser; Fiscal Year: 2012
    ..Telomerase activity and telomere length, cell aging measures, have clinical significance for health: a growing literature has linked lower levels of telomerase ..
  24. Regulation of yeast cellular aging through chromatin and novel pathways
    Weiwei Dang; Fiscal Year: 2013
    ..I expect to identify novel aging regulators that are either directly involved in chromatin biology or have direct targets in chromatin. ..
  25. ROS sensing and signaling in lifespan regulation
    Elizabeth A Schroeder; Fiscal Year: 2013
    ..Completion of this proposal will identify genes and processes that respond to mROS to regulate yeast lifespan, and may therefore identify targets for therapies and interventions to increase cellular lifespan and human health-span. ..
  26. Role of IbpA in maintaining viability of P. aeruginosa biofilm persister cells
    Michael J Franklin; Fiscal Year: 2012
    ..they are subject to other environmental stresses including oxidative stress from host defensive cells and cell aging. These stresses cause protein misfolding, inactivation, and aggregation...
  27. Stress-induced poor sleep: Sex differences, vulnerability &resilience factors
    Elissa S Epel; Fiscal Year: 2013
    ..We will efficiently piggyback the design and measures onto an already-funded R01 study on stress- induced cell aging that is currently following the sample of mothers...
  28. T Cell Homeostasis and Function in Immune Senescence
    Janko Nikolich-Zugich; Fiscal Year: 2012
    ..This application will investigate whether and how infections with latent herpesviruses contribute to T-cell aging and impair or benefit the immune defense...
  29. Epigenetic Regulation of Cell and Tissue Aging
    Nikolai A Timchenko; Fiscal Year: 2013
    ..If successful, our studies will help define a "histone code for cellular aging";and consequently open new avenues for interventions that target the human epigenome. ..
  30. DNA REPAIR, MUTATIONS AND CELLULAR AGING
    Jan Vijg; Fiscal Year: 2013
    ..All five projects together with the Animal and Pathology Core will jointly work on these topics, with their research plans fully integrated, yet maintaining their own, unique spheres of interest. ..
  31. Accelerated Biological Aging in Schizophrenia
    Gregory A Light; Fiscal Year: 2013
    ..Assessment of Insulin Resistance), inflammation (C-reactive protein), oxidative stress (F2-isoprostanes), and cell aging (telomere length), as well as a validated EEG-based marker of neurophysiological aging (mismatch negativity) ..
  32. Cigarette Smoke Induced Injury in Alveolar Cells in Model Systems
    Charles A Downs; Fiscal Year: 2010
    ..Perhaps cigarette smoking or secondary cigarette smoke induces cell aging in the young and predisposes children to the development of lung disease...
  33. The Tunicate Ciona: A New Model for the Effects of Aging on Tissue Regeneration
    William R Jeffery; Fiscal Year: 2013
    ..This study will develop the tunicate Ciona intestinalis, a vertebrate relative with powerful regeneration abilities that also recede with age, as a model to study the relationship between aging and tissue regeneration. ..
  34. Control of Telomere Heterochromatin by TERRA
    Paul M Lieberman; Fiscal Year: 2013
    ..The long-term goal of this proposal is to determine how telomeric heterochromatin is deregulated in cellular aging and cancer. ..
  35. Identifying Drugs to Treat Age-Dependent Neurodegeneration
    KIM DIANE FINLEY; Fiscal Year: 2012
    ..The goal of this proposal is to better understand the role of clearance pathways on aging and to develop in vivo assays that identify drugs that could be used for the treatment of human neurological disorders. ..
  36. DIETARY ETIOLOGIES OF HEART DISEASE AND CANCER
    Eric B Rimm; Fiscal Year: 2013
    ..LDL on macrophage and can now be measured in circulating plasma;2) Telomere length, a novel marker of somatic cell aging and oxidative damage that will be measured in circulating leukocytes and 3) Fluorescent oxidation products (FLOx)..
  37. T Cell Signaling in Rheumatoid Arthritis
    Jorg J Goronzy; Fiscal Year: 2013
    ..abstract_text> ..
  38. Broad H3K4me3 Domains: A Discovery Tool for Regulators of Neural Stem Cell Aging
    Elizabeth A Pollina; Fiscal Year: 2013
    ..in young and old NSCs, and, more generally will highlight the importance of broad H3K4m3 domains in adult stem cell aging. Understanding the mechanisms that preserve youthful NSC state be critical for identifying new avenues for ..
  39. Effects of Exercise on Cell Aging
    Elissa S Epel; Fiscal Year: 2013
    ..Lastly, this funding would allow us to save cells to test exploratory questions about cell aging. Specifically, if telomerase activity changes as expected, we can examine telomere length, and telomere ..
  40. The Regulation of Stem Cell Aging
    Sean J Morrison; Fiscal Year: 2013
    ..by repressing the JunB transcription factor and whether changes in JunB expression also regulate neural stem cell aging. Finally, we have discovered that the microRNA let-7b, which inhibits Hmga2 expression, increases its expression ..
  41. Effect of Genetic, Individual &Neighborhood Factors on Telomere Length
    Shannon Lynch; Fiscal Year: 2013
    ..This study will build the foundations of a conceptual model that can be used as the basis for future studies on aging. ..
  42. Reversing Epidermal Stem Cell Aging: Role of Bmi-1 and the Stem Cell Niche
    Ruby Ghadially; Fiscal Year: 2011
    ..we will study the roles of both intrinsic (Bmi-1/p16) and extrinsic/environmental influences on epidermal stem cell aging. In Aim 1 we will optimize and complete our assay of the differences between aged and young EpiSCs and then ..
  43. Social status, cellular aging, and mortality
    Elissa S Epel; Fiscal Year: 2012
    ..sample, it will provide data on the role of socioeconomic status within and across racial/ethnic groups and the interaction with genetic vulnerabilities in determining cell aging, and in turn, how cell aging predicts mortality.
  44. The Pathogenesis of Dyskeratosis Congenita
    Philip J Mason; Fiscal Year: 2013
    ..the pathogenesis of this disease and its susceptibility to cancer, and to identify novel targets for the development of new more specific therapies for patients with DC or related conditions associated with accelerated stem cell aging.
  45. Cell Aging in Major Depression
    Owen M Wolkowitz; Fiscal Year: 2013
    ..This in turn would yield new insights into the biology of depression and might spur the development of new treatments aimed at the molecular causes and consequences of depression. ..
  46. PRF 10th Anniversary Workshop on Progeria - "From Bench to Bedside in a Decade"
    Leslie B Gordon; Fiscal Year: 2010
    ....
  47. Identification of drugs that delay aging
    Kerry Kornfeld; Fiscal Year: 2013
    ..elegans as a model of stem cell aging. Studies conducted during the previous project period support three innovative hypotheses...
  48. Telomere Length as an Outcome in Lifespan Models of Personality and Health
    Sarah E Hampson; Fiscal Year: 2013
    ..This proposal builds on our provocative preliminary finding from this pilot work, namely that childhood Conscientiousness at age 10 predicted telomere length at age 50 in this selected group. ..
  49. SS peptides: improve mitochondrial and skeletal muscle function with age
    David J Marcinek; Fiscal Year: 2013
    ..This proposal tests a novel strategy for reversal of mitochondrial dysfunction in aged tissues that would represent a new paradigm for developing interventions to improve skeletal muscle function and quality of life in the elderly. ..
  50. Constructing gene-regulatory networks in yeast for a metabolic basis of lifespan
    John L Hartman; Fiscal Year: 2013
    ..Through interdisciplinary collaboration, we aim to deliver a systems level framework for CLS to help construct gene regulatory networks that can reveal mechanisms of cellular aging. ..
  51. Preconception and Prenatal Stress: Pathways to Child Biology and Behavior
    Christine Dunkel Schetter; Fiscal Year: 2013
    ..The findings have the potential to yield new understanding about the pervasive, serious maternal and child health disparities that extend throughout the lifespan and disproportionately impact low income, minority populations. ..
  52. Ex vivo rejuvenation and expansion of muscle stem cells from aged mice
    BENJAMIN DAVID COSGROVE; Fiscal Year: 2013
    ..and aid my development of an innovative, successful research program in the biology and treatment of stem cell aging. These activities will be mentored by Drs...
  53. Translational evaluation of aging, inflammation, and HIV in lung dysfunction
    Alison Morris; Fiscal Year: 2013
    ..lung function in HIV, to test the novel hypothesis that COPD in HIV is a manifestation of immune cell and lung cell aging, and to determine peripheral biomarkers of aging and inflammation in HIV COPD...
  54. Redox Biology of Quiescent Normal Fibroblasts and Epithelial Cancer Progression
    Prabhat C Goswami; Fiscal Year: 2013
    ....
  55. Roles of SIRT1 in normal hematopoietic and leukemic stem cells
    Wenyong Chen; Fiscal Year: 2013
    ..The proposed research is significant, because it is expected to shed insight on how SIRT1 plays a role in stem cell aging and tumorigenesis, and to develop a new strategy to eradicate resistant CML stem cells through modulating SIRT1 ..
  56. Immortal DNA Strand and Cardiac Stem Cell Aging
    Piero Anversa; Fiscal Year: 2013
    ..e., non-random DNA template segregation, will have to be determined to characterize the contribution of hCSC growth and differentiation to the development of the old failing heart. ..
  57. Telomeric Shortening, p53 and miR-34a Condition Senescence of Cardiac Progenitors
    Annarosa Leri; Fiscal Year: 2013
    ..We will focus on the interaction between p53, miR-34 and miR-34 target genes;miR-34 is a downstream effector of p53 and is proposed to be an important determinant of CPC and cardiac aging. ..
  58. Aging and Reprogramming of Somatic Cells to Pluripotency
    Peter J Hornsby; Fiscal Year: 2010
    ....
  59. Molecular Regulation of Stem Cell Aging
    Thomas A Rando; Fiscal Year: 2013
    ..the biology of aging, specifically focused on the molecular characteristics, mechanisms and consequences of stem cell aging. Based on mutual interests and complementary areas of expertise, the three laboratories of this Program form a ..
  60. The role of p16INK4a in mammalian aging
    Norman E Sharpless; Fiscal Year: 2013
    ..In specific aim I, we propose to further define the role of p16INK4a in pancreatic -cell aging using a novel p16INK4a-conditional allele generated in our lab...
  61. Histone Modifications Associated w/Senescence in Arabidopsis
    JUDY ANN BRUSSLAN; Fiscal Year: 2012
    ..Another goal of this pilot proposal is to increase the research competitiveness of the PI via an ongoing mentoring relationship with a successful epigenome researcher at a nearby R01 university. ..
  62. Regulation of Hematopoietic Stem Cell Aging by the E3 ubiquitin Ligase Fbw7
    LINSEY BLAIR REAVIE; Fiscal Year: 2011
    ..This work will also address how these pathways may impact age related diseases such as chronic myelogenous leukemia. ..
  63. Chronic and Acute Psychosocial Stress and Impaired Cell Aging
    Elissa Epel; Fiscal Year: 2009
    ..We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo...
  64. ANTI-GAL IGG ON HUMAN RED CELLS: A MODEL FOR CELL AGING
    Uri Galili; Fiscal Year: 1993
    ..3Ga1 beta1>AGlcNac-R epitopes exposed de novo in the course of normal or pathologic red cell aging. To gain further information on the molecules interacting with anti-Gal, we studied the expression of Gal alpha1&..
  65. Antioxidant Defense System and Leydig Cell Aging
    Haolin Chen; Fiscal Year: 2007
    ..The first aim of the proposal is to describe parameters of Leydig cell aging in the mouse by testing the hypotheses that, with aging, testosterone production by Leydig cells of C57BL/6 mice ..
  66. METABOLISM AND FUNCTION IN THE AGING ADRENAL GLAND
    JEROME KOWAL; Fiscal Year: 1993
    ..The aging adrenal gland can provide a system for obtaining a more generalized understanding of how lipid oxidation may affect physiologic function in aging cells...
  67. GENOMIC STABILITY AND AGING IN YEAST
    Steven Brill; Fiscal Year: 2003
    ..abstract_text> ..
  68. RESEARCH TRAINING IN GERIATRIC MEDICINE
    JEROME KOWAL; Fiscal Year: 2000
    ..This program has attracted superior postdoctoral trainees to aging research, stimulated collaborative efforts in aging research, increased our faculty pool and heightened visibility of geriatrics and gerontologic research at CWRU. ..
  69. YEAST CHROMOSOME STRUCTURE, REPLICATION AND SEGREGATION
    Victoria Lundblad; Fiscal Year: 2000
    ..Our objective for this meeting is to continue the extremely high level of excitment and scientific excellence that has characterized the past five conferences. ..