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Research Paper|Volume 2, Issue 10|pp 709—726

Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence

Martin Weinberger1, Ana Mesquita2, Timothy Carroll1, Laura Marks1, Hui Yang3, Zhaojie Zhang3, Paula Ludovico2, William C. Burhans1
  • 1Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
  • 2Instituto de Investigação em Ciências da Vida e Saúde (ICVS), Escola de Ciências da Saúde, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
  • 3Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA
Received: October 14, 2010Accepted: October 25, 2010Published: October 27, 2010
https://doi.org/10.18632/aging.100215

Copyright: © 2010 Weinberger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes.