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.
