Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous

Szu-Chieh Mei; Charles Brenner

doi:10.1371/journal.pbio.1002048

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Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous

Journal article

Open access

Peer reviewed

Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous

Szu-Chieh Mei and Charles Brenner

PLoS biology, Vol.13(1), e1002048

01/2015

DOI: 10.1371/journal.pbio.1002048

PMCID: PMC4310591

PMID: 25633578

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Abstract

In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

Gene Expression Regulation, Fungal

Saccharomyces cerevisiae - cytology

Culture Media, Conditioned

Saccharomyces cerevisiae - physiology

Silent Information Regulator Proteins, Saccharomyces cerevisiae - physiology

Sirtuin 2 - physiology

Caloric Restriction

Glucose - metabolism

Microbial Viability

Details

Title: Subtitle: Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous
Creators: Szu-Chieh Mei - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Charles Brenner - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PLoS biology, Vol.13(1), e1002048
DOI: 10.1371/journal.pbio.1002048
PMID: 25633578
PMCID: PMC4310591
NLM abbreviation: PLoS Biol
ISSN: 1544-9173
eISSN: 1545-7885
Publisher: United States
Language: English
Date published: 01/2015
Academic Unit: Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9983788599702771

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