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Why the fuss over R.O.S.?

     Attempts to prolong longevity have been a major endeavor in science and several hypotheses have been proposed about the major causes.  Scientists have focused on the role of reactive oxygen species in longevity through investigations using mice models. Reactive oxygen species’ role in aging processes is also known as the free radical theory of aging.  Scientists have found that reactive oxygen species attack molecules of biological systems and are the main cause for the functional decline of organ systems that lead to eventual death.  Various experiments were conducted to investigate the role of reaction oxygen species using transgenic mouse models.

     Specifically, the purpose of these experiments are to determine if minimizing the level of ROS (reactive oxygen species) in certain organelles in mice have any effect on the overall health and lifespan of the mouse.  The hypothesis was tested by amplifying a certain gene in mouse DNA that expresses catalase, an enzyme that breaks down the ROS’s.  However, prior to beginning the experiments, transgenic mice are necessary for the experimentation.

Development of a Transgenic Mouse

     A transgenic mouse is a mouse that has had a specific gene, in this case the human catalase gene, inserted into its genome.  In these experiments, transgenic mice were created using pronuclear microinjection.  In this method, the gene is put into the nucleus of an egg, and then inserted into a surrogate mother, who has been conditioned to believe it is pregnant.  A number of the new pups will carry this gene and over-express the human catalase gene in certain organelles of their cells, depending on where the gene was placed in the genome.  Using these transgenic mice, the role of ROS in longevity was investigated.3

Background and Role of Reactive Oxygen Species

     Most of the stability of a molecule comes from the number and pairing of electrons in the orbitals.  Reactive oxygen species, also called free radicals, are molecules containing the element hydrogen that have one or more electrons in their outermost orbital that lack a pair of electrons.1   These types of molecules can be hazardous to cellular health, not only because they tend to react with molecules in cell structures, but can also cause a kind of chain reaction.  ROS’s tend to pass on their unpaired electron to adjacent molecules, which in turn pass the unpaired electron along to another molecule and so on.  As each new molecule receives the electron, the molecule’s shape, binding tendencies, and function can change, altering and hindering function.2  The detrimental effects of this electron passing vary depending on the molecule.  However, most molecules in the human biological system are fairly susceptible to these, making the chain effect disadvantageous.

     ROS’s are formed in various ways, but have been found to be produced mostly in the mitochondrial respiratory chain.  The leakage of some electrons from the chain is unavoidable, and from there they go directly to react with oxygen molecules to form a reactive super-oxide anion O2-.  Fortunately, cells create their own enzymes in order to break down ROS’s into stable forms.  Superoxide dismutase, for example, breaks down the dangerous O2- into the less harmful hydrogen peroxide, H202.  In fact, most enzymes that break down ROS’s convert the molecules into H2O2 and the role of enzyme catalase is revealed.  Catalase, an enzyme that catalyzes the decomposition of hydrogen peroxide into water and oxygen, completes the neutralization of detrimental ROS’s.2  The catalase used in this experiment is a human catalase gene that has been transgenically imposed into the mouse genome.

     To learn more about the specific aspects of the research methods, experiments, and individual results, feel free to explore the website for further insight into this theory of reactive oxygen species on prolonging the life of transgenic mice models.


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University of Arizona
Biology 181H 2005 Group 7
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Last Revised: 12/7/05