L11 - SC in ageing and cancer

Question 1

What causes SC ageing?

Answer 1

Telomere shortening, energy metabolism, ROS and DNA damage

All lead to senescence

Question 2

What happens during telomere shortening?

Answer 2

T-loop at telomere - telomere shorten with every round of replication
When t-loop is lost cell recog as DSB - SENES

Question 3

How do ROS affect SC?

Answer 3

By products of OP can damaged mt and nuc DNA
ROS levels increase in HSCs with age
Antiox increase rep potent of HSCs

Question 4

What does senescence require?

Answer 4

Activation of Rb and p53

Question 5

What are the two models of SC and cancer?

Answer 5

Stoichastic model
- All tumour cells are equipotent
- Some cells prolif and increase tumour growth, others differentiate
CSC model
- Tumours are heirarchically ordered
- CSCs contribute to the long term growth
- Prog have limited growth potential

Question 6

How would you test the models for SC and cancer?

Answer 6

If stoich - all cells can form tumour
If CSC - only certain cells can
Graft cells into nude mice - analyse tumour growth

Question 7

What are the implications of the CSC model for therapy?

Answer 7

Target CSCs for apop
Target CSCs for differentiation
combination of both