Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

Mei, Szu Chieh; Brenner, Charles

doi:10.1371/journal.pbio.1002048

Cited by 21 publications

(11 citation statements)

References 30 publications

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“…S2–3). It is important to note that microfluidics-based lifespan measurements are free from potential non-cell autonomous effects while results obtained from the micromanipulator-based lifespan assay can be a combination of both cell autonomous and non-cell autonomous effects (Mei and Brenner, 2015), as during the application of the micromanipulator, cells can be exposed to small molecules that may be secreted to the solid growth surface during aging.…”

Section: Resultsmentioning

confidence: 99%

Yeast Replicator: A High-Throughput Multiplexed Microfluidics Platform for Automated Measurements of Single-Cell Aging

2015

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The yeast Saccharomyces cerevisiae is a model organism for replicative aging studies; however, conventional lifespan measurement platforms have several limitations. Here we present a microfluidics platform that facilitates simultaneous lifespan and gene expression measurements of aging yeast cells. Our multiplexed high-throughput platform offers the capability to perform independent lifespan experiments using different yeast strains or growth media. Using this platform in minimal media environments containing glucose, we measured the full lifespan of individual yeast cells in wild-type and canonical gene deletion backgrounds. Compared to glucose, in galactose we observed a 16.8% decrease in replicative lifespan accompanied by a ~2-fold increase in single-cell oxidative stress levels reported by PSOD1-mCherry. Using PGAL1-YFP to measure the activity of the bistable galactose network, we saw that OFF and ON cells are similar in their lifespan. Our work shows that aging cells are committed to a single phenotypic state throughout their lifespan.

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Section: Resultsmentioning

confidence: 99%

Yeast Replicator: A High-Throughput Multiplexed Microfluidics Platform for Automated Measurements of Single-Cell Aging

2015

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“…The blueprints for multFYLM, as well as the image analysis pipeline are both available via GitHub (see Materials and methods). We note that microfluidics-based lifespan measurements are free from potential extrinsic effects (e.g., secretion of small molecules onto the solid agar surface) which have been proposed to confound observations of RLS assays using manual microdissection ( Mei and Brenner, 2015 ). Using the multFYLM, we set out to determine whether fission yeast undergoes replicative aging.…”

Section: Discussionmentioning

confidence: 99%

“…This is traditionally done via manual micro-dissection of sibling cells on agar plates, a laborious process that is especially difficult and error-prone for symmetrically dividing fission yeast. Extrinsic effects related to using a solid agar surface may confound observations made under these conditions ( Mei and Brenner, 2015 ). Finally, recent work using high-throughput microfluidic devices to study individual budding yeast and bacterial cells ( Lee et al, 2012 ; Crane et al, 2014 ; Wang et al, 2010 ; Liu et al, 2015 ; Jo et al, 2015 ; Nobs and Maerkl, 2014 ; Tian et al, 2013 ; Huberts et al, 2014 ; Minc and Chang, 2010 ) has shown that large sample sizes are needed to truly capture cellular lifespan accurately – populations less than ~100 cells do not reliably estimate the RLS ( Huberts et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

An aging-independent replicative lifespan in a symmetrically dividing eukaryote

Spivey

Jones

Rybarski

et al. 2017

eLife

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The replicative lifespan (RLS) of a cell—defined as the number of cell divisions before death—has informed our understanding of the mechanisms of cellular aging. However, little is known about aging and longevity in symmetrically dividing eukaryotic cells because most prior studies have used budding yeast for RLS studies. Here, we describe a multiplexed fission yeast lifespan micro-dissector (multFYLM) and an associated image processing pipeline for performing high-throughput and automated single-cell micro-dissection. Using the multFYLM, we observe continuous replication of hundreds of individual fission yeast cells for over seventy-five generations. Surprisingly, cells die without the classic hallmarks of cellular aging, such as progressive changes in size, doubling time, or sibling health. Genetic perturbations and drugs can extend the RLS via an aging-independent mechanism. Using a quantitative model to analyze these results, we conclude that fission yeast does not age and that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.DOI: http://dx.doi.org/10.7554/eLife.20340.001

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“…We also developed FYLM Critic, an image-processing pipeline for quantitative phenotypic analysis of individual cell lineages. We note that microfluidics-based lifespan measurements are free from potential extrinsic effects (e.g., secretion of small molecules onto the solid agar surface) which have been proposed to confound observations of RLS assays using manual microdissection (56). Using the multFYLM, we set out to determine whether fission yeast undergoes replicative aging.…”

Section: Discussionmentioning

confidence: 99%

An aging-independent replicative lifespan in a symmetrically dividing eukaryote

Spivey

Jones

Rybarski

et al. 2016

Preprint

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The replicative lifespan (RLS) of a cell-defined as the number of cell divisions before death-has informed our understanding of the mechanisms of cellular aging. However, little is known about aging and longevity in symmetrically dividing eukaryotic cells because most prior studies have used budding yeast for RLS studies. Here, we describe a multiplexed fission yeast lifespan micro-dissector (multFYLM) and an associated image processing pipeline for performing high-throughput and automated single-cell micro-dissection. Using the multFYLM, we observe continuous replication of hundreds of individual fission yeast cells for over seventy-five generations. Surprisingly, cells die without the classic hallmarks of cellular aging, such as progressive changes in size, doubling time, or sibling health. Genetic perturbations and drugs can extend the RLS via an aging-independent mechanism. Using a quantitative model to analyze these results, we conclude that fission yeast does not age and that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.

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Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

Abstract: Calorie-restriction extends lifespan in many multicellular organisms; here substances secreted by calorie-restricted yeast are found to induce longer life in other yeast cells, suggesting that cellular communication is a component of this phenomenon even in a single-celled organism.

Cited by 21 publications

References 30 publications

Yeast Replicator: A High-Throughput Multiplexed Microfluidics Platform for Automated Measurements of Single-Cell Aging

Yeast Replicator: A High-Throughput Multiplexed Microfluidics Platform for Automated Measurements of Single-Cell Aging

An aging-independent replicative lifespan in a symmetrically dividing eukaryote

An aging-independent replicative lifespan in a symmetrically dividing eukaryote

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