Abstract:
The free-radical theory of aging proposes that intracellular accumulation of oxidative damage caused by
reactive oxygen species (ROS) is responsible for the process of senescence. ROS are produced during
normal aerobic metabolism and have been shown to cause numerous cellular and sub-cellular defects
that lead to termination of the cell cycle and, in extreme cases, to apoptosis (cell death). Previous
research has suggested that important antioxidant enzymes and other low molecular weight
antioxidants may exhibit differential levels of expression throughout the day/night cycle. These
expression trends appear to be under the control of biological clock genes, which interact to generate
circadian rhythms within organisms. There are several clock genes that are essential for proper clock
function in Drosophila melanogaster, the most important of which are period (per) and timeless (tim); a
null mutation in either of these genes causes a loss of clock function in the organism. Since biological
rhythms regulate many important processes, they may be involved in the antioxidant defense system.
The overarching hypothesis of this study was that the loss of biological rhythmicity exhibited by mutant
flies may render them more susceptible to the negative effects associated with ROS exposure. The main
objective of the current study was to investigate the intersection of circadian rhythmicity, oxidative
stress, and the process of aging in Drosophila. We show that period mutants have increased
susceptibility to oxidative stress, when compared to their wildtype (CSP) counterparts, indicating that
the period gene is somehow involved in the oxidative stress response system. However, experiments on
the enzyme catalase show that one rhythmically expressed enzyme cannot explain the physiological
response exhibited by the organism. Accumulation of oxidative damage, as measured by protein
carbonylation, appears to be rhythmic, suggesting a possible explanation for the differential
susceptibility to exogenous oxidative stress.
