Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging.

Authors: Koc A; Gasch AP; Rutherford JC; Kim HY; Gladyshev VN

Abstract: Aging is thought to be caused by the accumulation of damage, primarily from oxidative modifications of cellular components by reactive oxygen species (ROS). Here we used yeast methionine sulfoxide reductases MsrA and MsrB to address this hypothesis. In the presence of oxygen, these antioxidants could increase yeast lifespan and did so independent of the lifespan extension offered by caloric restriction. However, under ROS-deficient, strictly anaerobic conditions, yeast lifespan was shorter, not affected by MsrA or MsrB, and further reduced by caloric restriction. In addition, we identified changes in the global gene expression associated with aging in yeast, and they did not include oxidative stress genes. Our findings suggest how the interplay between ROS, antioxidants, and efficiency of energy production regulates the lifespan. The data also suggest a model wherein factors implicated in aging (for example, ROS) may influence the lifespan yet not be the cause of aging.

Keywords: Anaerobiosis; Antioxidants/metabolism; Caloric Restriction; Cell Aging/genetics/*physiology; Methionine Sulfoxide Reductases; Oligonucleotide Array Sequence Analysis; Oxidation-Reduction; Oxidative Stress; Oxidoreductases/genetics/*metabolism; Oxygen/metabolism; RNA, Fungal/genetics/metabolism; RNA, Messenger/genetics/metabolism; Reactive Oxygen Species/*metabolism; Saccharomyces cerevisiae/*cytology/*enzymology/genetics/metabolism; Saccharomyces cerevisiae Proteins/genetics/metabolism
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 101
Issue: 21
Pages: 7999-8004
Date: May 14, 2004
PMID: 15141092
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Citation:

Koc A, Gasch AP, Rutherford JC, Kim HY, Gladyshev VN (2004) Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging. Proceedings of the National Academy of Sciences of the United States of America 101: 7999-8004.


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