stem cells and aging

Question 1

what are some of the characteristics of aging?

Answer 1

• low tissue turnover
• wounds heal more slowly
• more inflammation and scarring

Question 2

where is stem cell contribution high?

Answer 2

• tissues with high turnover and high regeneration such as the blood and gut
• medium contribution in cells with low turnover but high regeneration such as the liver

Question 3

where is stem cell contribution low

Answer 3

in organs with low cell turnover and low regeneration such as the brain and kidney

Question 4

What are the 3 hypotheses for how stem cells contribute to aging?

Answer 4

1) decreasing numbers contribute to aging
2) change in capacity contributes to ageing
3) altered stem cell environment contributes to aging

Question 5

How do stem cells contribute in the muscle?

Answer 5

following injury, satellite cells are activated and divide to fill the space to form new muscle cells. there are fewer satellite cells in old muscle fibres so their numbers must decrease with age. satellite cell morphology remains the same and their differentiation remains the same - issue is in their numbers/division

Question 6

What is notch-delta signalling?

Answer 6

required for proper formation of the first skeletal muscle cells in the embyro
regulates the proliferation and differentiation of muscle satellite cells
declines in old muscle

Question 7

Describe notch-delta signalling in muscle

Answer 7

• Delta protein resides on the satellite cell, notch on the muscle fibre with an external and internal domain
• in response to injury, the domains attach to one another and the extracellular domain of notch is cleaved
• this starts a signalling cascade that leads to the rebuilding of muscle fibre

Question 8

How does age affect notch-delta signalling?

Answer 8

• increased signalling in young muscle
• decreased delta expression in old muscle makes it less able to respond to injury
• artificial notch activation in old muscle leads to regeneration such as in young muscle
• may be due to a lack of signals causing regeneration and satellite cell replication

Question 9

What happens if you give an old mouse a young mouse’s blood supply?

Answer 9

• injuries in the old mouse benefit from the young mouse blood - signs of regeneration not normally seen in old mice
• injuries in the young mouse are not affected by old mouse blood and regenerate as usual
• could be due to factors in the mouse blood or due to cell migration

Question 10

How did they determine what int he young mouse blood was aiding regeneration?

Answer 10

• tagged young cells with GFP
• looked for GFP+ cells in the old mouse tissue
• no cells were found
• must therefore be due to factors in the blood aiding delta acitvation - IGF1?