Cell size and growth rate are major determinants of replicative lifespan

Yang, Jianbo; Dungrawala, Huzefa; Hua, Hui; Manukyan, Aram; Abraham, Lesley; Lane, Wesley; Mead, Holly B.; Wright, Jill; Schneider, Brandt L.

doi:10.4161/cc.10.1.14455

Cited by 141 publications

(182 citation statements)

References 52 publications

(140 reference statements)

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“…6b) and predicted that mother cells should increase their volume in each generation ( Fig. 6c) as experimentally observed 13,49 . Moreover, the pedigree analysis produced steady-state cell size distributions very similar to the experimental data obtained in different nutritional conditions (Fig.…”

Section: Cell Size At Start Is Dictated By Volume Growth Rate In G1supporting

confidence: 75%

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

et al. 2012

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Budding yeast cells are assumed to trigger start and enter the cell cycle only after they attain a critical size set by external conditions. However, arguing against deterministic models of cell size control, cell volume at start displays great individual variability even under constant conditions. Here we show that cell size at start is robustly set at a single-cell level by the volume growth rate in G1, which explains the observed variability. We find that this growth-rate-dependent sizer is intimately hardwired into the start network and the Ydj1 chaperone is key for setting cell size as a function of the individual growth rate. mathematical modelling and experimental data indicate that a growth-rate-dependent sizer is sufficient to ensure size homeostasis and, as a remarkable advantage over a rigid sizer mechanism, it reduces noise in G1 length and provides an immediate solution for size adaptation to external conditions at a population level.

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Section: Cell Size At Start Is Dictated By Volume Growth Rate In G1supporting

confidence: 75%

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

et al. 2012

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“…S7). Although an inverse correlation between cell size and lifespan has been reported (27), the underlying molecular mechanism causing these changes in cell cycle time and cell size remains poorly understood.…”

Section: Resultsmentioning

confidence: 99%

“…Cells that began budding at a smaller size had a longer remaining lifespan, whereas cells that began budding at a larger size had a shorter lifespan. The effect of cell size and growth rate on replicative lifespan has been reported for various mutants (27). Large-cell mutants grew proportionally faster and had a shorter lifespan than small-cell mutants.…”

Section: Resultsmentioning

confidence: 99%

High-throughput analysis of yeast replicative aging using a microfluidic system

Liu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

156

174

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Saccharomyces cerevisiae has been an important model for studying the molecular mechanisms of aging in eukaryotic cells. However, the laborious and low-throughput methods of current yeast replicative lifespan assays limit their usefulness as a broad genetic screening platform for research on aging. We address this limitation by developing an efficient, high-throughput microfluidic single-cell analysis chip in combination with high-resolution time-lapse microscopy. This innovative design enables, to our knowledge for the first time, the determination of the yeast replicative lifespan in a highthroughput manner. Morphological and phenotypical changes during aging can also be monitored automatically with a much higher throughput than previous microfluidic designs. We demonstrate highly efficient trapping and retention of mother cells, determination of the replicative lifespan, and tracking of yeast cells throughout their entire lifespan. Using the high-resolution and large-scale data generated from the high-throughput yeast aging analysis (HYAA) chips, we investigated particular longevity-related changes in cell morphology and characteristics, including critical cell size, terminal morphology, and protein subcellular localization. In addition, because of the significantly improved retention rate of yeast mother cell, the HYAA-Chip was capable of demonstrating replicative lifespan extension by calorie restriction.microfluidics | high-throughput | replicative aging | calorie restriction | Saccharomyces cerevisiae

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“…130 Other studies have indicated a strong correlation between cell size and cycle time. 131,132 In general, conditions that elongate cell cycle times tend to produce small cells. These correlations suggest the possibility of a link between cell cycle time/cell size and lifespan.…”

Section: Cell Cycle Control At the Crossroads Of Reproduction And Deathmentioning

confidence: 99%

“…These correlations suggest the possibility of a link between cell cycle time/cell size and lifespan. 132 Initial aging studies in yeast reported that a dramatic increase in cell size (hypertrophy) accompanies aging in yeast. 132,133 Nevertheless, a potential causative role for cell size in aging was ruled out when an early study demonstrated that cell enlargement with alpha pheromone did not result in a shortened lifespan.…”

Section: Cell Cycle Control At the Crossroads Of Reproduction And Deathmentioning

confidence: 99%

A budding yeast's perspective on aging: The shape I'm in

Smith

Wright

Schneider

2015

Exp Biol Med (Maywood)

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Aging is exemplified by progressive, deleterious changes that increase the probability of death. However, while the effects of age are easy to recognize, identification of the processes involved has proved to be much more difficult. Somewhat surprisingly, research using the budding yeast has had a profound impact on our current understanding of the mechanisms involved in aging. Herein, we examine the biological significance and implications surrounding the observation that genetic pathways involved in the modulation of aging and the determination of lifespan in yeast are highly complicated and conserved.

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Cell size and growth rate are major determinants of replicative lifespan

Cited by 141 publications

References 52 publications

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

High-throughput analysis of yeast replicative aging using a microfluidic system

A budding yeast's perspective on aging: The shape I'm in

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