1. Previously 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

2. Organism requires cell proliferation and cell death Why/ When would an organism need cell proliferation? Why/When would an organism need cell death?

3. Have discussed cell growth– what’s cell death Programmed cell death= apoptosis vs Necrosis Compare and contrast

4. Apoptosis: The movie CBI 17.1

5. Vesicles do not travel between cells Cell fragments ‘bleb’ and are engulfed by Other cells.

6. 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

7. Caspase cascade: the animation Apoptosis animation Forming the apoptosome cytochrome c Apaf-1 Caspase 9 ATP

8. Families of proteins are involved Bcl-2, Bcl-X L –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)

9. Must have correct amount of each, at the appropriate time It’s a balancing act Proliferation Cell death Proliferation Cell death

10. 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 multifactorial (big surprise =^) ) but all point to problems with DNA

11. 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.

12. What remains You have the prefinal questions work on them!!! Final exam available on Monday 12/4 –2 parts I. Cumulative, from prefinal questions II. ‘Third review’ Werner’s/Cellcycle Lab Article Portfolio: Due before Noon Tuesday 12/5: 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 11th BEFORE 9am (can be turned in separately)