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Lecture 23.docx

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Western University
Biology 1002B
Tom Haffie

Lecture 23: Oxygen and Aging  Progressive impairment of function with an increasing probability of death o Factors are environmental, metabolic, genetics o Life expectancy has increased over the years 1800s 28yrs to 2000 73 yrs  Reactive oxygen species (ROS) o ROS implicated in aging o Paradox of aerobic life o O2 -> superoxide -> hydrogen peroxide -> hydroxyl radical -> H2O o Catalase superoxide mutase  Mitochondria: major source of ROS o Cytochrome oxidase donates electrons to oxygen  Partially reduced forms, like ROS (can be created by donating o Cytochrome oxidase donates 4 electrons at a time,  If it donates 1 at a time, then there will be a lot of ROS created and mitochondria will not exist o Thus, cytochrome oxidase is not a source of ROS o Ubiquitin in the ETC can create ROS o Sometimes, there’s electron leaks, and this can create ROS, happens at Q pool o SOD1 converts superoxide to hydrogen peroxide o Catalase gets rid of the hydrogen peroxide o ROS is Unavoidable, because a lot of electrons are moving at a very high speed o Disease that are linked to mitochondria and ROS  Some Parkinson’s disease linked to complex 1, the NADH dehydrogenase  ALS amyotrophic lateral sclerosis some are linked to SOD1, doesn’t make enough or not efficient enough  Cytochrome complex mutation o Caenorhabditis elegans (C. elegans) – worm o Mutation – cytochrome complex (less efficient) o The more oxygen in the environment, the mutants will not survive, they don’t live as long as non-mutants  mitDNA genotype and longevity o Japanese centenarians (genetics?) o Complex 1 (NADH dehydrogenase) and complex 5 (ATP synthase) and mitochondrial ribosomes  The centenarians have a higher incidence among those, and ribosome structures are different  The mitochondrial ROS theory of Aging o Aging linked to decrease in mitochondrial function o ROS -> DNA damage -> mitochondrial dysfunction -> ROS (cycle) o It’s not as clean cut as this, doesn’t explain everything, but explains something  Mitochondria and PCD o Intrinsic program  Metabolic triggers  ROS  Effects of Hyperoxia o Higher than normal amounts o Drosophila raised in normal and 100% O2  Normoxia have normal mitochondria  Hyperoixa have swirls in their mitochondria  “swirl” phenomenon – oxidative stress  Old
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