Divergent Aging of Isogenic Yeast Cells Revealed through Single-Cell Phenotypic Dynamics.

Cellular Senescence Computational Biology Computer Simulation DNA Replication Microfluidics Models, Biological Saccharomyces cerevisiae / genetics Single-Cell Analysis
caloric restriction cell fate decision cellular aging computational modeling dynamics microfluidics single-cell analysis sirtuins stochastic simulations time-lapse microscopy

Journal

Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080

Informations de publication

Date de publication:
27 03 2019
Historique:
received: 29 06 2018
revised: 28 11 2018
accepted: 07 02 2019
pubmed: 11 3 2019
medline: 16 5 2020
entrez: 11 3 2019
Statut: ppublish

Résumé

Although genetic mutations that alter organisms' average lifespans have been identified in aging research, our understanding of the dynamic changes during aging remains limited. Here, we integrate single-cell imaging, microfluidics, and computational modeling to investigate phenotypic divergence and cellular heterogeneity during replicative aging of single S. cerevisiae cells. Specifically, we find that isogenic cells diverge early in life toward one of two aging paths, which are characterized by distinct age-associated phenotypes. We captured the dynamics of single cells along the paths with a stochastic discrete-state model, which accurately predicts both the measured heterogeneity and the lifespan of cells on each path within a cell population. Our analysis suggests that genetic and environmental factors influence both a cell's choice of paths and the kinetics of paths themselves. Given that these factors are highly conserved throughout eukaryotes, divergent aging might represent a general scheme in cellular aging of other organisms.

Identifiants

DOI: 10.1016/j.cels.2019.02.002 PMID: 30852250 PMC: PMC6514117
pubmed: 30852250
pii: S2405-4712(19)30036-5
doi: 10.1016/j.cels.2019.02.002
pmc: PMC6514117
mid: NIHMS1023628
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

242-253.e3

Subventions

Organisme : NIGMS NIH HHS
ID : P50 GM085764
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056440
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM069811
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Meng Jin (M)

BioCircuits Institute, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.

Yang Li (Y)

Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.

Richard O'Laughlin (R)

Department of Bioengineering, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.

Philip Bittihn (P)

BioCircuits Institute, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.

Lorraine Pillus (L)

Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, San Diego, CA 92093, USA; UCSD Moores Cancer Center, University of California, San Diego, La Jolla, San Diego, CA 92093, USA.

Lev S Tsimring (LS)

BioCircuits Institute, University of California, San Diego, La Jolla, San Diego, CA 92093, USA. Electronic address: ltsimring@ucsd.edu.

Jeff Hasty (J)

BioCircuits Institute, University of California, San Diego, La Jolla, San Diego, CA 92093, USA; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, San Diego, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, San Diego, CA 92093, USA. Electronic address: jhasty@eng.ucsd.edu.

Nan Hao (N)

BioCircuits Institute, University of California, San Diego, La Jolla, San Diego, CA 92093, USA; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, San Diego, CA 92093, USA. Electronic address: nhao@ucsd.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Sciences de l'information › Informatique › Biologie informatique › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Technologie, industrie et agriculture › Technologie › Miniaturisation › Microtechnologie › Microfluidique › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Divergent Aging of Isogenic Yeast Cells...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Divergent Aging of Isogenic Yeast Cells...