Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence.

EMBO Reports
Monika Barroso-VilaresElsa Logarinho

Abstract

Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy-prone mouse models uncovered an unanticipated link between CIN and aging. Using young to old-aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age-associated CIN. We found that elderly cells have an increased number of stable kinetochore-microtubule (k-MT) attachments and decreased efficiency in the correction of improper k-MT interactions. Chromosome mis-segregation rates in old-aged cells decreased upon both genetic and small-molecule enhancement of MT-depolymerizing kinesin-13 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence. Therefore, we provide mechanistic insight into age-associated CIN and disclose a strategy for the use of a small-molecule to inhibit age-associated CIN and to delay the cellul...Continue Reading

References

Oct 1, 1995·Mutation Research·J F Stone, A A Sandberg
Nov 1, 1995·The Journal of Cell Biology·Y ZhaiG G Borisy
Sep 18, 1996·Mechanisms of Ageing and Development·A B MukherjeeS Thomas
Aug 25, 1997·Experimental Cell Research·A B Mukherjee, S Thomas
Apr 30, 2003·The Journal of Cell Biology·Claire DitchfieldStephen S Taylor
Feb 10, 2004·Nature Cell Biology·Michael A LampsonTarun M Kapoor
Jul 19, 2005·Trends in Cell Biology·Daniela Cimini, Francesca Degrassi
Jun 1, 2007·Molecular Biology of the Cell·Amity L ManningDuane A Compton
Jun 29, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Birgit MoschThomas Arendt
Dec 9, 2008·Nature Cell Biology·Samuel F BakhoumDuane A Compton
Sep 3, 2010·Current Opinion in Cell Biology·Duane A Compton
Dec 27, 2011·Current Opinion in Cell Biology·Samuel F Bakhoum, Duane A Compton
Jun 19, 2012·Nature Reviews. Genetics·So I NagaokaPatricia A Hunt
Jan 9, 2013·Methods in Molecular Biology·Francis Rodier
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Dec 18, 2013·The Journal of Cell Biology·Eric C SwansonJeanne B Lawrence
May 23, 2014·Nature·Jan M van Deursen
Dec 10, 2015·Nature Medicine·Bennett G ChildsJan M van Deursen
Feb 4, 2016·Nature·Darren J BakerJan M van Deursen
Oct 30, 2016·Science·Bennett G ChildsJan M van Deursen
May 24, 2017·Proceedings of the National Academy of Sciences of the United States of America·Hui YangZhijian J Chen
Jun 11, 2017·Advances in Experimental Medicine and Biology·Joana Catarina MacedoElsa Logarinho
Jul 25, 2017·Nature·Karen J MackenzieAndrew P Jackson
Aug 2, 2017·Nature Cell Biology·Selene GlückAndrea Ablasser
Aug 22, 2017·Nature Medicine·Joshua N FarrSundeep Khosla
Aug 29, 2017·Current Biology : CB·Alejandra Hernandez-SeguraMarco Demaria
Oct 5, 2017·Nature·Zhixun DouShelley L Berger
Jan 18, 2018·Nature·Samuel F BakhoumLewis C Cantley
Jan 30, 2018·Frontiers in Immunology·Tamas FulopClaudio Franceschi
May 1, 2018·Current Biology : CB·Danica DrpicHelder Maiato
May 26, 2018·Nature Communications·Damian DudkaPatrick Meraldi
Jul 22, 2018·Nature Communications·Joana Catarina MacedoElsa Logarinho
Jan 4, 2019·Nature Cell Biology·Salah MahmoudiAnne Brunet
Feb 24, 2019·International Journal of Molecular Sciences·Sofia Melo PereiraElsa Logarinho
May 19, 2019·Mechanisms of Ageing and Development·Monika Barroso-Vilares, Elsa Logarinho

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Citations

Apr 30, 2020·EMBO Reports·Laura Tovini, Sarah E McClelland
Jan 2, 2021·Ageing Research Reviews·Eva PrašnikarAndrej Perdih
Jan 13, 2021·Nature Reviews. Cancer·Anand VasudevanJason M Sheltzer
Dec 5, 2020·Pharmacology & Therapeutics·Ibrahim Y AbdelgawadBeshay N Zordoky
Jun 3, 2021·Cells·Ivan Y IourovSergei I Kutsev

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Methods Mentioned

BETA
PCR
electrophoresis
Profiler
dot blots
chip

Software Mentioned

ImageJ
[UNK] RNA
Ion Torrent
Fiji
GraphPad
Transcriptome Analysis Console
Quantity one I ‐ D Analysis
coverageAnalysis
Andor IQ
CFX Maestro

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