Senescence and Ageing Flashcards
1
Q
What are telomeres?
A
- Repetitive DNA sequences at the ends of all human chromosomes
- Contain thousands of repeats of nucleotide sequence (TTAGGG)
- 46 CHROMOSOMES/ 92 TELMOERES
2
Q
What do telomeres do?
A
- protect chromosomes
- separate one chromosome from another in the DNA sequence
- prevent chromosome fusion leading to genomic instability
3
Q
What is the end replication problem?
A
- One strand replicates to the end
- 5 end and 3 end
- Other strand has a 8-12 gap at the 5’ end
- Each chromosome in a dividing cell progressively shortens = chromosomes shortening
- genes are lost from the ends
4
Q
What is the function of telomeres?
A
- T length = regulates how many times an individual cell can divide
- Telomeric sequence shorten each time the DNA replicates
- provide a means for counting cell division
THINK OF THE END OF A SHOE LACE TO STOP IT UNRAVELLING
5
Q
How are telometes linked to ageing (and cancer)?
A
- once the telomer shrinks to a certain level= can no longer divide
- ## Metabolism slows down, it ages and dies = sensecence
6
Q
What is the molecular clock mechanism of ageing?
A
- A clock thst counts the number of times a cell has divided when telomeres are short, cellular senescence (growth arrest occurs)
7
Q
What is the hayflick limit?
A
- Cells are only capable of a limited number of population doublings in culture
8
Q
What does doubling in vitro mean?
A
Replication going on in culture dishes
9
Q
What triggers cellular senescence?
A
- when cells acquire one or a few critically short telomeres
- Telomeres shorten from 10-15 Kb (germ line) to 3-5 kb after 50-60 doublings (average lengths of TRFS)
10
Q
What is telomerase?
A
- A ribonucleoprotein enzyme complex that has been referred to as a cellular immortalizing enzyme
- Stabilises telomere length by adding hexameric DNA repeats onto the telomeric ends of the chromosomes, compensating for the erosion of telomeres that occurs in its abscence
11
Q
How do telomerase work?
A
- Adding back telomeric DNA to the ends of chromosomes, compensating for the loss of telomeres that normally occurs as cells divide
- Most somatic cells do not express this enzyme and thus lose telomeres with each division
- Active in germ cells , in vitro immortalised cells, cancer cells and some stem cells
- High telomerase activity exists in these cells = fast turnover
12
Q
What is an immortal cell?
A
-Cells with their telomerase switched on e.g blood cells and cancer cerlls
-Cancer cells do not age because they produce telomerase
13
Q
Explain the process of cellular senescence
A
- Once telomere shrinks to a certain extent = cells stop dividing
- (~4kb in humans)
- Leads to cell morphology changes
- Gene expression changes etc
- Can be measured by biomarkers
