The radical consequences of respiration: reactive oxygen species in aging and disease

Lectures: 1 session / week, 2 hours / session

7.03 Genetics
7.05 General Biochemistry
7.06 Cell Biology
or
7.28 Molecular Biology

The emergence of oxygen was responsible for the origin of much of life as we know it, coinciding with the evolution of eukaryotic and multicellular organisms. However, environmental oxygen was highly toxic to almost an entire subset of species, namely the anaerobes, making oxygen arguably the most fatal pollutant in the existence of the Earth. To deal with the damaging effects of oxygen radicals generated during mitochondrial respiration, aerobic organisms have had to develop protective mechanisms, such as antioxidant enzymes, redox regulatory proteins and repair pathways. At controlled levels, reactive oxygen species (ROS) perform important biological functions, for example acting as signal transducers in mitogenic pathways and in mediating the immune inflammatory response. However, excessive levels of oxygen radicals have been implicated in a wide array of human diseases, ranging from premature aging to cancer. In this course, we will discuss the physiological consequences of oxidative stress and altered ROS levels, with emphasis on understanding the complex dual role of ROS as both cellular signaling molecules and cellular damaging agents. To understand how we are protected from the intrinsic reactivity of oxygen, we will start with a survey of basic oxygen radical biochemistry followed by a discussion of the mechanisms of action of cellular as well as dietary antioxidants. After considering the normal physiological roles of oxidants, we will examine the effects of elevated ROS and a failure of cellular redox capacity on the rate of organismal and cellular aging as well as on the onset and progression of several major diseases that are often age-related. Topics will include ROS-induced effects on stem cell regeneration, insulin resistance, heart disease, neurodegenerative disorders and cancer. The role of antioxidants in potential therapeutic strategies for modulating ROS levels will also be discussed.

This course consists of 12 classes and will involve the discussion of two papers from the primary literature per session with the emphasis on class discussion. No lectures will be given. You will find that the role of ROS in different pathologies is often a source of lively debate within the scientific community, and frequently the assigned reading will be chosen to reflect this fact. Active class participation is both encouraged and expected. The papers must be read in detail in advance of each session. A brief introduction will be given to the topics and papers to be discussed during the end of the previous session. Students will lead the discussions for the papers that deal with the pathologies of oxidative stress.

This course is designed to give you insight into the complex role of oxygen radicals in normal cell physiology and in causing the cellular damage implicated in a number of diseases. The assigned literature is intended to familiarize you with the scientific approaches used and to provide you with a general overview of the field.

Oxidative glucose metabolism substrates (a.k.a. cookies) and antioxidants (fruits and chocolate) will be regularly provided.

This course is graded pass/fail, and the grade depends on attendance, participation, and the successful completion of two assignments.

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