Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling.

Marina Musa,Anita Lovrić,Nuno Raimundo,Ana Šarić,Andrea Nikolić,Anita Kriško,Ira Milosević,Marina Rudan,Sandra Sobočanec,Peter Bou Dib,Kristian Vlahoviček,Matea Perić

doi:10.18632/aging.101560

Abstract

Heat-induced hormesis is a well-known conserved phenomenon in aging, traditionally attributed to the benefits conferred by increased amounts of heat shock (HS) proteins. Here we find that the key event for the HS-induced lifespan extension in budding yeast is the switch from glycolysis to respiratory metabolism. The resulting increase in reactive oxygen species activates the antioxidant response, supported by the redirection of glucose from glycolysis to the pentose phosphate pathway, increasing the production of NADPH. This sequence of events culminates in replicative lifespan (RLS) extension, implying decreased mortality per generation that persists even after the HS has finished. We found that switching to respiratory metabolism, and particularly the consequent increase in glutathione levels, were essential for the observed RLS extension. These results draw the focus away solely from the HS response and demonstrate that the antioxidant response has a key role in heat-induced hormesis. Our findings underscore the importance of the changes in cellular metabolic activity for heat-induced longevity in budding yeast.

Highlights

While in the laboratory setting the growth conditions are strictly maintained, cells and organisms in the wild are subject to a wide range of different environmental conditions, from changing temperature to inconsistent nutrient availability
Mild transient heat shock causes metabolic reprogramming and lifespan extension Budding yeast S. cerevisiae go through a limited number of cell divisions before the onset of senescence, producing daughter cells, the number of which constitutes their replicative lifespan (RLS)
The heat exposure started at the mother cells replicative age of 1-3 generations and lasted for 3 hours, after which they were returned to optimal growth temperature of 30oC

Summary

Introduction

While in the laboratory setting the growth conditions are strictly maintained, cells and organisms in the wild are subject to a wide range of different environmental conditions, from changing temperature to inconsistent nutrient availability. Some of these conditions can be lethal if severe or prolonged, but a vast majority promotes an adaptive response when transient and sufficiently mild. This dose response is known as hormesis. It has been observed that low levels of one stressor can protect against more than one type of stress. Low levels of oxidative stress protect against subsequent exposure to toxins such as cyanide, making hormesis “cross-modal” [6, 7]

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