Cellular Senescence as a Cause of Senescent Pathology Flashcards
What is the Hayflick limit?
Point of replicative senescence
Which cell cycle stage are most cells in in vivo>
G1 cell cycle arrest
What is cellular senesence in terms of the cell cycle and how does this differ from non-senescent cells?
In senescent cells G1 permanent
In non-senescent cells G1 not permanent - signals take them out
What can be used as a senescent cell marker and why?
SA-beta-gal
Senescent cells have increased galactosidase activity
How does the number of senescent cells in human tissues change with age?
Increases
Name the triggers of cellular senescence
End replication problem
DNA damage
Oncogene activation
Developmental program
What is the end replication problem and how does it cause senescence?
Linear chromosomes cannot be perfectly replicated - DNA polymerase leaves gap at 3’ end
Telomerase constructs 3’ ends - telomeres
Low telomerase levels in most cells
Telomeres shorten until too short - triggers senescence
What is the effect of oncogene activation and how does it cause senescence?
Drives cellular proliferation
Hyperactivity blocked by cell defence mechanisms - triggers senescence
What is the effect of senescence triggers acting via different pathways?
Activate different multiple cell cycle inhibitors - act on common mediators - trigger senescence
Name 2 cell cycle inhibitors
p53
p16
What is the effect of p16?
Inhibits common mediators - inhibit RB - triggers senescence
How does the same gene encode p15, p16, and p19?
Using different promoters
Name the 3 properties of senescent cells
Cell cycle arrest
Resistance to apoptosis
Senescence-associated secretory phenotype (SASP)
How many pathways are there to cause cell cycle arrest and which cell cycle inhibitors do they involve?
2
p16, p53
What is the effect of cycle cycle arrest?
Stops cell replication
