Journal ArticleDOI
Telomeres and telomerase: three decades of progress.
Jerry W. Shay,Woodring E. Wright +1 more
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TLDR
This Timeline article highlights the key advances that have expanded the views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease.Abstract:
Many recent advances have emerged in the telomere and telomerase fields. This Timeline article highlights the key advances that have expanded our views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease. Three decades ago, the classic view was that telomeres protected the natural ends of linear chromosomes and that telomerase was a specific telomere-terminal transferase necessary for the replication of chromosome ends in single-celled organisms. While this concept is still correct, many diverse fields associated with telomeres and telomerase have substantially matured. These areas include the discovery of most of the key molecular components of telomerase, implications for limits to cellular replication, identification and characterization of human genetic disorders that result in premature telomere shortening, the concept that inhibiting telomerase might be a successful therapeutic strategy and roles for telomeres in regulating gene expression. We discuss progress in these areas and conclude with challenges and unanswered questions in the field.read more
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Cellular Senescence: Defining a Path Forward
Vassilis G. Gorgoulis,Peter D. Adams,Andrea Alimonti,Dorothy C. Bennett,Oliver Bischof,Cleo L. Bishop,Judith Campisi,Manuel Collado,Konstantinos Evangelou,Gerardo Ferbeyre,Jesús Gil,Eiji Hara,Valery Krizhanovsky,Diana Jurk,Andrea B. Maier,Masashi Narita,Laura J. Niedernhofer,João F. Passos,Paul D. Robbins,Clemens A. Schmitt,John M. Sedivy,Konstantinos Vougas,Thomas von Zglinicki,Daohong Zhou,Manuel Serrano,Marco Demaria +25 more
TL;DR: A consensus from the International Cell Senescence Association (ICSA) is presented, defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers.
Journal ArticleDOI
The regulation and functions of DNA and RNA G-quadruplexes.
TL;DR: This Review discusses the identification of G4s and evidence for their formation in cells using chemical biology, imaging and genomic technologies, and discusses the connection between G4 formation and synthetic lethality in cancer cells, and recent progress towards considering G 4s as therapeutic targets in human diseases.
Journal ArticleDOI
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Ruchi Kumari,Parmjit S Jat +1 more
TL;DR: In this article, the molecular mechanisms that underlie cellular senescence and the senescent associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.
Journal ArticleDOI
Overcoming cancer therapeutic bottleneck by drug repurposing
TL;DR: This review presents various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono- or drug combination therapy.
Journal ArticleDOI
Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players
TL;DR: Critical mechanisms activating TERT transcription are summarized, with special emphases on the contribution of TERT promoter mutations and structural alterations at the TERT locus, and the underlying implications of these genomic events-driven TERT hyperactivity in cancer initiation/progression and potential clinical applications are discussed.
References
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Journal ArticleDOI
The serial cultivation of human diploid cell strains.
Leonard Hayflick,P.S. Moorhead +1 more
TL;DR: A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.
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Specific association of human telomerase activity with immortal cells and cancer
Nam Woo Kim,Mieczyslaw A. Piatyszek,Karen R. Prowse,Calvin B. Harley,Michael D. West,Peter L. C. Ho,Gina M. Coviello,Woodring E. Wright,Scott L. Weinrich,Jerry W. Shay +9 more
TL;DR: A highly sensitive assay for measuring telomerase activity was developed in this paper, which showed that telomerases appear to be stringently repressed in normal human somatic tissues but reactivated in cancer, where immortal cells are likely required to maintain tumor growth.
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The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI
Telomeres shorten during ageing of human fibroblasts.
TL;DR: The amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo.
Journal ArticleDOI
Extension of life-span by introduction of telomerase into normal human cells
Andrea G. Bodnar,Michel M. Ouellette,Maria Frolkis,Shawn E. Holt,Choy-Pik Chiu,Gregg B. Morin,Calvin B. Harley,Jerry W. Shay,Serge Lichtsteiner,Woodring E. Wright +9 more
TL;DR: In this article, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomere catalytic subunit.