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International Journal of Molecular SciencesVolume 20, Issue 4, 2 February 2019, Article number 938

Approaches towards longevity: Reprogramming, senolysis, and improved mitotic competence as anti-aging therapies(Review)(Open Access)

  • aAgeing and Aneuploidy Laboratory, IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4200-135, Portugal
  • bI3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal
  • cCell Division Unit, Faculty of Medicine, Department of Experimental Biology, Universidade do Porto, Porto, 4200-319, Portugal

Abstract

Mainstream approaches that are currently used as anti-aging therapies primarily explore the senescence and epigenetic drift aging hallmarks and they are at two ends of the spectrum. While senolytic therapies include either the selective elimination of senescent cells or the disruption of their secretome with the use of drugs or natural compounds, cellular reprogramming uses genetic manipulation to revert cells all the way back to pluripotency. Here, we describe the progress that has been made on these therapies, while highlighting the major challenges involved. Moreover, based on recent findings elucidating the impact of mitotic shutdown and aneuploidy in cellular senescence, we discuss the modulation of mitotic competence as an alternative strategy to delay the hallmarks of aging. We propose that a regulated rise in mitotic competence of cells could circumvent certain limitations that are present in the senolytic and reprogramming approaches, by acting to decelerate senescence and possibly restore the epigenetic landscape. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Author keywords

AgingCell cycle fitnessCellular reprogrammingCellular senescence

Indexed keywords

EMTREE medical terms:acute lymphoblastic leukemiaAlzheimer diseaseaneuploidyantiaging activityatherosclerosisautophagybreast cancercell agingchromosomal instabilitychromosome aberrationdegenerative diseaseDNA methylationDNA modificationDown syndromegene expressionhumanhypercholesterolemiain vitro fertilizationinduced pluripotent stem cellinflammatory bowel diseaselongevitynuclear reprogrammingosteoporosispluripotent stem cellReviewsenescencestem cell nichetelomereanimalcell aginggene therapygenetic epigenesisgeneticslongevitymitosisprocedures
MeSH:AnimalsCellular ReprogrammingCellular SenescenceEpigenesis, GeneticGenetic TherapyHumansLongevityMitosis

Funding details

Funding sponsor Funding number Acronym
IF/00916/2014,PD/BD/128000/2016
China National Funds for Distinguished Young ScientistsPTDC/BEX-BCM/2090/2014
2020/PORTUGAL 2020
Ministério da Ciência, Tecnologia e Ensino SuperiorSuperior
POCI,NORTE-01-0145-FEDER-000029,POCI-01-0145-FEDER-031120,PTDC/BIA-CEL/31120/2017
E.L. Wiegand Foundation
European Regional Development Fund
NORTE2020,POCI-01-0145-FEDER-007274

  • 1

    Funding: E.L. holds an FCT Investigator Postdoctoral Grant (IF/00916/2014) and R.R. holds an FCT Fellowship PD/BD/128000/2016 from FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior). The following project grants supported this work: National Funds through FCT under the project PTDC/BEX-BCM/2090/2014; European Regional Development Fund (FEDER) through the COMPETE 2020—Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and National funds through FCT in the framework of the project POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/2017); NORTE-01-0145-FEDER-000029 funded by North Regional Operational Program (NORTE2020) under PORTUGAL 2020 Partnership Agreement through FEDER; and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/PORTUGAL 2020 through FEDER and by FCT.

  • ISSN: 16616596
  • Source Type: Journal
  • Original language: English
  • DOI: 10.3390/ijms20040938
  • PubMed ID: 30795536
  • Document Type: Review
  • Publisher: MDPI AG

  Logarinho, E.; Cell Division Unit, Faculty of Medicine, Department of Experimental Biology, Universidade do Porto, Porto, Portugal;
© Copyright 2019 Elsevier B.V., All rights reserved.

Cited by 1 document

Barroso-Vilares, M. , Logarinho, E.
Chromosomal instability and pro-inflammatory response in aging
(2019) Mechanisms of Ageing and Development
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