Death by transposition - the enemy within?
John M. Sedivy,Jill A. Kreiling,Nicola Neretti,Marco De Cecco,Steven W. Criscione,Jeffrey W. Hofmann,Xiaoai Zhao,Takahiro Ito,Abigail L. Peterson +8 more
TLDR
The hypothesis is developed that the derepression of endogenous retrotransposable elements (RTEs) – “genomic parasites” – is an important and hitherto under‐unexplored molecular aging process that can potentially occur in most tissues and contribute to age‐associated tissue degeneration and pathology.Abstract:
Here we present and develop the hypothesis that the derepression of endogenous retrotransposable elements (RTEs) - "genomic parasites" - is an important and hitherto under-unexplored molecular aging process that can potentially occur in most tissues. We further envision that the activation and continued presence of retrotransposition contribute to age-associated tissue degeneration and pathology. Chromatin is a complex and dynamic structure that needs to be maintained in a functional state throughout our lifetime. Studies of diverse species have revealed that chromatin undergoes extensive rearrangements during aging. Cellular senescence, an important component of mammalian aging, has recently been associated with decreased heterochromatinization of normally silenced regions of the genome. These changes lead to the expression of RTEs, culminating in their transposition. RTEs are common in all kingdoms of life, and comprise close to 50% of mammalian genomes. They are tightly controlled, as their activity is highly destabilizing and mutagenic to their resident genomes.read more
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Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
TL;DR: Coppe et al. as mentioned in this paper showed that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy, including interleukin (IL)-6 and IL-8.
Journal ArticleDOI
Epigenetics and aging.
Sangita Pal,Jessica K. Tyler +1 more
TL;DR: Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process, and inhibitors of epigenetic enzymes can influence life span of model organisms.
Journal ArticleDOI
Interventions to Slow Aging in Humans: Are We Ready?
Valter D. Longo,Adam Antebi,Andrzej Bartke,Nir Barzilai,Holly M. Brown-Borg,Calogero Caruso,Tyler J. Curiel,Rafael de Cabo,Claudio Franceschi,David Gems,Donald K. Ingram,Thomas E. Johnson,Brian K. Kennedy,Cynthia Kenyon,Samuel Klein,John J. Kopchick,G Lepperdinger,Frank Madeo,Mario G. Mirisola,James R. Mitchell,Giuseppe Passarino,Karl Lenhard Rudolph,John M. Sedivy,Gerald S. Shadel,David A. Sinclair,David A. Sinclair,Stephen R. Spindler,Yousin Suh,Jan Vijg,Manlio Vinciguerra,Luigi Fontana,Luigi Fontana +31 more
TL;DR: There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age and their potential to be safe and effective in extending human healthspan.
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TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets
TL;DR: This method shows improved recovery of TE transcripts over other published expression analysis methods, in both synthetic data and qPCR/NanoString-validated published datasets.
Journal ArticleDOI
Restricting retrotransposons: a review
TL;DR: This review examines the strategies the cell has evolved to coexist with these genomic “parasites”, focussing on the non-long terminal repeat retrotransposons of humans and mice, and considers potential pitfalls in interpreting Retrotransposon-related data.
References
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TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Journal ArticleDOI
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison,Randy Strong,Zelton D Sharp,James F. Nelson,Clinton M. Astle,Kevin Flurkey,Nancy L. Nadon,J. Erby Wilkinson,Krystyna Frenkel,Christy S. Carter,Christy S. Carter,Marco Pahor,Marco Pahor,Martin A. Javors,Elizabeth Fernandez,Richard A. Miller +15 more
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.
Journal ArticleDOI
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
Jean-Philippe Coppe,Christopher K. Patil,Francis Rodier,Francis Rodier,Yun-Yu Sun,Denise P. Muñoz,Denise P. Muñoz,Joshua Goldstein,Peter S. Nelson,Pierre-Yves Desprez,Pierre-Yves Desprez,Judith Campisi,Judith Campisi +12 more
TL;DR: 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 is suggested.
Journal ArticleDOI
Clearance of p16 Ink4a -positive senescent cells delays ageing-associated disorders
Darren J. Baker,Tobias Wijshake,Tamar Tchkonia,Nathan K. LeBrasseur,Bennett G. Childs,Bart van de Sluis,James L. Kirkland,Jan M. van Deursen +7 more
TL;DR: 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.
Journal ArticleDOI
CpG Islands and the Regulation of Transcription
Aimee M. Deaton,Adrian Bird +1 more
TL;DR: Vertebrate CpG islands are generically equipped to influence local chromatin structure and simplify regulation of gene activity.
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