Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging.
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.
Koc
Ahmet
A
Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
Gasch
Audrey P
AP
Rutherford
Julian C
JC
Kim
Hwa-Young
HY
Gladyshev
Vadim N
VN
D000693:Anaerobiosis; D000975:Antioxidants / Q000378:metabolism; D031204:Caloric Restriction; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D051150:Methionine Sulfoxide Reductases; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D012331:RNA, Fungal; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C487504:MsrA protein, S cerevisiae; C027219:methionine sulfoxide reductase; C487505:MXR2 protein, S cerevisiae; D010100:Oxygen