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Hypotheses to explain cell life span Free radical theory…….. DNA damage DNA replication problems (WRN)…. DNA damage Telomere ‘clock’ ….. Length and ….. DNA damage Austriaco and Guarente paper Manipulate the length of yeast telomeres
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Hypotheses to explain cell life span Free radical theory…….. DNA damage DNA replication problems (WRN)…. DNA damage Telomere ‘clock’ ….. Length and ….. DNA damage Austriaco and Guarente paper Manipulate the length of yeast telomeres What was the effect on yeast lifespan Previously
Organism requires cell growth and cell death Why/ When would an organism need cell growth (proliferation)? Why/When would an organism need cell death?
Have discussed cell growth– what’s cell death Programmed cell death= apoptosis vs Necrosis Compare and contrast
Apoptosis: The movie http://www.youtube.com/watch?v=V-NsR-krKME Vesicles do not travel between cells Cell fragments ‘bleb’ and are engulfed by other cells.
How does this all happen? • Lack of survival factors • Lack of growth factors to bind with growth factor receptors) • Presence of Death activators • Receive death signals to bind with death receptors (TNF, Fas ligand) • Internal signal due to damage (p53) Results in activation of Caspase cascade
Caspase cascade: the animation Apoptosis animation Forming the apoptosome cytochrome c Apaf-1 Caspase 9 ATP http://www.youtube.com/watch?v=9KTDz-ZisZ0&feature=related
Families of proteins are involved Bcl-2, Bcl-XL –Anti-apoptotic Bad– apoptosis promoter (inhibits a death inhibitor) Bax, Bak– stimulate release of cyt. c IAP family– inhibitors of apoptosis (bind procaspases block activation, binds caspases and inhibits activity)
It’s a balancing act Must have correct amount of each, at the appropriate time Cell death Proliferation Cell death Proliferation
So what have we learned? • Cells must have input from environment • Cells must be able to integrate internal and external signals and cues • Differential gene expression plays big role • ‘Cause’ of aging multi-factorial (big surprise) but all point to problems with DNA
We’ve seen all of this before (Think Graves’, Bipolar, yeast mating) Science is an ongoing process-- The research builds and requires interpretation based on comparison with controls and current understanding of the system. Progress (like cell proliferation) is rarely linear. Requires checkpoints, repeating steps and integration of signals from other researchers.
What remains • You have the prefinal questions work on them!!! • Final exam available on Monday 12/7 • 2 parts I. Cumulative, from prefinal questions II. ‘Third review’ Werner’s/Cellcycle • Lab Article Portfolio: Due before 5PM Friday Dec 4th: Includes Hard copy of I. Final revised version II. Individual editing efforts (what you wrote before you revised someone else’s section) BOTH parts of FINAL due MONDAY December 14th BEFORE noon (can be turned in separately)