Ch. 10: Eternal Life Flashcards
Most normal cells have a limited number of times
they can…
divide
Most human cells are a little more complex, but they
also have limited…
proliferative potential
If you take human cells out of the body and put them in a petri dish…
* They will…
continue to divide…
* And then they will stop dividing
senescence
when cells stop dividing and cannot divide again even when in an environment that favors growth.
* They exit the cell cycle irreversibly.
replicative senescence
is 1 type of senescence due to cells reaching their maximum
number of cell divisions.
Human cells will undergo stress-associated senescence mediated through …
the RB pathway
Cells with high levels of
physiological stress will increase levels of
p16
p16 will inhibit…
progression through G1 phase by inhibiting CyclinD-CDK4/6
(RB will never be phosphorylated and cells will never be able to go
past the R checkpoint.)
* Therefore…
cells with high p16 will
become senescent.
Human cells also undergo replicative senescence
mediated through…
the TP53 pathway
Cells with genomic damage
(including damage due to short telomeres) will increase levels of…
TP53
TP53 will inhibit…
progression through late G1 and early S by inhibiting active CyclinE-CDK2 and CyclinA-CDK2
- Therefore, cells with high TP53 will become senescent.
(“Replicative senescence”).
What happens if human cells in culture lose TP53?
- Cells will undergo crisis:
- Widespread genomic
alterations/chaos. - Apoptosis is induced.
- Image on the right: Cell
population in crisis
refractile cells
catch the light and appear white- represent cell fragments in the middle of apoptosis.
How do human cells become immortal?
1- inhibit RB pathway (allows them to avoid stress associated senescence)
* 2- could inhibit TP53 (allows them to avoid replicative senescence)
* 3- avoid genomic crisis/apoptosis (how do they do this?)
* Find a way to avoid genomic crisis due to short telomeres.