Uncoupling reproduction from metabolism extends chronological lifespan in yeast

Authors

Saisubramanian Nagarajan, University of Montana
Arthur L. Kruckeberg, University of Montana
Karen H. Schmidt, University of Montana
Evgueny Kroll, University of Montana
Morgan Hamilton, University of Montana
Kate McInnerney, Montana State University
Ryan Summers, Utah State University
Timothy Taylor, Utah State University
Frank Rosenzweig, University of Montana

Document Type

Article

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

4-15-2014

Volume

111

Issue

15

Disciplines

Biology | Life Sciences

Abstract

Studies of replicative and chronological lifespan in Saccharomyces cerevisiae have advanced understanding of longevity in all eukaryotes. Chronological lifespan in this species is defined as the agedependent viability of nondividing cells. To date this parameter has only been estimated under calorie restriction, mimicked by starvation. Because postmitotic cells in higher eukaryotes often do not starve, we developed a model yeast system to study cells as they age in the absence of calorie restriction. Yeast cells were encapsulated in a matrix consisting of calcium alginate to form ~3 mm beads that were packed into bioreactors and fed ad libitum. Under these conditions cells ceased to divide, became heat shock and zymolyase resistant, yet retained high fermentative capacity. Over the course of 17 d, immobilized yeast cells maintained 10%. Immobilized cells exhibited a stable pattern of gene expression that differed markedly from growing or starving planktonic cells, highly expressing genes in glycolysis, cell wall remodeling, and stress resistance, but decreasing transcription of genes in the tricarboxylic acid cycle, and genes that regulate the cell cycle, including master cyclins CDC28 and CLN1. Stress resistance transcription factor MSN4 and its upstream effector RIM15 are conspicuously up-regulated in the immobilized state, and an immobilized rim15 knockout strain fails to exhibit the long-lived, growth-Arrested phenotype, suggesting that altered regulation of the Rim15-mediated nutrient-sensing pathway plays an important role in extending yeast chronological lifespan under calorie-unrestricted conditions.

Keywords

Ca-Alginate encapsulation, Cell longevity

DOI

https://doi.org/10.1073/pnas.1323918111

Comments

Freely available online through the PNAS open access option.

Recommended Citation

Nagarajan, Saisubramanian; Kruckeberg, Arthur L.; Schmidt, Karen H.; Kroll, Evgueny; Hamilton, Morgan; McInnerney, Kate; Summers, Ryan; Taylor, Timothy; and Rosenzweig, Frank, "Uncoupling reproduction from metabolism extends chronological lifespan in yeast" (2014). Biological Sciences Faculty Publications. 436.
https://scholarworks.umt.edu/biosci_pubs/436