Diverse conditions support near-zero growth in yeast: Implications for the study of cell lifespan

Abstract

Baker's yeast has a finite lifespan and ages in two ways: a mother cell can only divide so many times (its replicative lifespan), and a non-dividing cell can only live so long (its chronological lifespan). Wild and laboratory yeast strains exhibit natural variation for each type of lifespan, and the genetic basis for this variation has been generalized to other eukaryotes, including metazoans. To date, yeast chronological lifespan has chiefly been studied in relation to the rate and mode of functional decline among non-dividing cells in nutrient-depleted batch culture. However, this culture method does not accurately capture two major classes of long-lived metazoan cells: cells that are terminally differentiated and metabolically active for periods that approximate animal lifespan (e.g. cardiac myocytes), and cells that are pluripotent and metabolically quiescent (e.g. stem cells). Here, we consider alternative ways of cultivating Saccharomyces cerevisiae so that these different metabolic states can be explored in non-dividing cells: (i) yeast cultured as giant colonies on semi-solid agar, (ii) yeast cultured in retentostats and provided sufficient nutrients to meet minimal energy requirements, and (iii) yeast encapsulated in a semisolid matrix and fed ad libitum in bioreactors. We review the physiology of yeast cultured under each of these conditions, and explore their potential to provide unique insights into determinants of chronological lifespan in the cells of higher eukaryotes.

Uncoupling growth and succinic acid production in an industrial Saccharomyces cerevisiae strain

“…With respect to the industrial application of the zero‐growth concept, the use of membrane filters to achieve cell retention might be less feasible on an industrial scale, as blocking of effluent filters could prevent long‐time operation. Alternative means of cell retention could involve the use of fast‐sedimenting yeast mutants (Oud et al, 2013) or cell immobilization (Gulli et al, 2019; Nagarajan et al, 2014). Near‐zero growth conditions can also be achieved by controlling the feed of a limiting nutrient in fed‐batch processes.…”

Quantitative physiology and proteome adaptations of Bifidobacterium breve NRBB57 at near-zero growth rates

“…CC-BY 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted September 6, 2022. ; https://doi.org/10.1101/2022.09.06.506712 doi: bioRxiv preprint Retentostat studies have shown the importance of this system in elucidating the mechanisms involved in survival of microbial cells in environments with extremely low nutrient availability (4,10,(12)(13)(14)(15)(16)(17). In these conditions, microbial cells use different strategies to adapt to the nutritional stress in order to survive.…”

“…Retentostat studies have shown the importance of this system in elucidating the mechanisms involved in survival of microbial cells in environments with extremely low nutrient availability (4,10,(12)(13)(14)(15)(16)(17). In these conditions, microbial cells use different strategies to adapt to the nutritional stress in order to survive.…”

Uncoupling growth and succinic acid production in an industrial Saccharomyces cerevisiae strain

“…Use of membrane filters to achieve cell retention might be less feasible on an industrial scale as blocking of effluent filters could prevent long-time operation. Alternative means of cell retention could involve use of fastsedimenting yeast mutants (Oud et al, 2013) or immobilization (Gulli et al, 2019;Nagarajan et al, 2014) might be explored. Near zero growth conditions can also be achieved by controlling the feed of a limiting nutrient in fed-batch processes.…”