The Living End: Lifespan and Cell Death

Question 1

necrosis

Answer 1

Necrosis: death by unknown or unforeseen factors.
Uncontrolled cell death
Leaking cells may damage surrounding tissues with inflammation (pro-inflammatory cytokines)
Necrotic lesions may seen blackness and rotting tissues
Passive (no ATP)

Question 2

steps of necrosis

Answer 2

Damage to cell membrane and loss of membrane strength
Toxins, temperature etc.
Cell swells and puts stress on the membrane
Cell membrane breaks and cellular content leaks out (immune system reacts and inflammation damages tissues)

Question 3

apoptosis

Answer 3

Apoptosis: genetically programmed cell death. 
Active process (ATP)
Avoids inflammation

Question 4

steps of apoptosis

Answer 4

Steps:
DNA becomes fragmented; it condenses and becomes more visible (nucleus becomes darker)
Cell shrinks
Membrane blebs which break off and are phagocytosed by phagocytes

Question 5

a simple model in C.elegans

Answer 5

Simple eukaryote (caspases have different names but using mammalian ones for ease)
Short lifespan (20 days)
Cells are preprogrammed from birth to death - easily tracked
BH3 binds to the mitochondrion which blocks Bcl-2 (present on mitochondria membrane)
ApaF1 (pro-caspase 3) is released when Bcl-2 and BH3 bind
Caspases are enzymes that attack proteins (produced in a pro protein so that it is inactivated)
Cleaving of caspase activates it (get rid of pro)
ApaF1 cleaves pro-caspase 3 to form caspase 3
Caspase 3 degrades other proteins

Executioner caspase: caspase 3 etc. break down proteins in the cell.

Initiator caspase: activate caspases and start cascades (ApaF1)

Question 6

apoptosis in vertebrates

Answer 6

Two pathways (only one in c.elegens)

Question 7

extrinsic pathway

Answer 7

Activated by external signals
FAS ligand on signal cell binds to FAS receptor on target cell
Inactive caspase 8 (pro) comes up to bottom of FAS receptor and is cleaved
DISC (death inducing signalling complex) is formed and releases activated (initiator) caspase 8
Caspase 8 activates caspase 3,6,7 (executioner)

Question 8

intrinsic pathway

Answer 8

Activated by intracellular signals
Usually preprogrammed
Protein signal activates release of cytochrome c from mitochondria
BAX or BAK transporter proteins move cytochrome c into the cytoplasm
Cytochrome c binds to ApaF 1 and activates it, forming an apoptosome
Caspase 9 is inactive but is activated by binding to the apoptosome
Caspase 9 activates executioner caspases 3,6,7

Question 9

Bcl 2 control

Answer 9

Can bind to Bak and Bax preventing release of cytochrome c

Anti-apoptotic regulator

Question 10

IAPs control

Answer 10

Inhibitors of apoptosis
Bind to activated caspases and inhibit function
Constituently expressed in the cell - minimum threshold for apoptosis is set

Question 11

apoptosis and the cell cycle

Answer 11

P53 at end of G1 phase
Responsible for making sure there are no mutations before moving to the next stage
If mutations are present, p53 activates apoptosis
P53 is activated by phosphorylation
Binds to two pro-apoptotic mediators (puma and noxa - promote release of cytochrome c)

Question 12

apoptosis in development

Answer 12

Getting rid of webbing between fingers - targeted apoptosis

Question 13

apoptosis and disease

Answer 13

Heart disease - cells after heart attacks are stressed and undergo apoptosis - weak heart and cardiac death
cancer - unregulated cell growth, not enough death
Some viral infections - latency is where viruses prevent apoptosis so they can live in the cell or they will promote apoptosis so they can spread

Question 14

telomere attraction theory

Answer 14

DNA polymerase runs out of things to hold onto in replication
Telomeres allow for genes not to be lost
Telomeres get shorter with every generation
Eventually they are so short that they are no longer able to maintain the integrity of the chromosome and p53 causes apoptosis
Bodies possess telomerase which can increase length of telomeres (not produced in every cell)
Telomerase is active in cancerous cells

Question 15

replicative senescence

Answer 15

Stress-induced premature senescence theory
As you get older you get more mutations
Overtime the mutations hit a critical point and our cells are no longer viable

Question 16

why do organisms have different lifespans?

Answer 16

Mice have longer telomeres than we do
Smaller animals are more prone to predation - must reproduce more quickly
After reproduction there is no selective pressure to maintain life

Question 17

antagonistic pleiotropy theory

Answer 17

mutations that were positive become negative in later life
Increased testosterone would improve reproductive fitness when young
Could get premature prostate cancer when older - only happens after reproduction so not evolved to survive this

Question 18

mutation accumulation theory

Answer 18

Overtime we get so many that out cells die
Our bodies can no longer fix
Happens after the person has reproduced (selection shadow - life span is not increased to reproduce more, no point to fix them)