Cell Determination And Cell Senescence

Question 1

Define cell determination

Answer 1

When the cell fate becomes stable. It’s followed by differentiation. When a cell chooses a particular fate, it is said to be determined

Question 2

Give the differences between cell determination and cell differentiation

Answer 2

Determination =portions of the genome are selected for differentiation
=occurs in totipotent, embryonic stem cells
= a result of asymmetric segregation of cytoplasmic determinants
= responsible for assigning the fate of the cells
Differentiation = specialisation of a cell
= follows cell determination
= a result of differential gene expression
= responsible for function specialisation

Question 3

Why does asymmetrical cell division happen?

Answer 3

The uneven distribution of cytoplasmic molecules (proteins or mRNAs) within a cell before it divides

Question 4

What causes cell determination?

Answer 4

• inductive signals from neighbouring cells
• one group of cells influences the development of another group of cells
• pioneer factors

Question 5

Define cellular senescence

Answer 5

Irreversible process in all cells arrest mechanism in which cells cease to divide

Question 6

Why does cellular senescence happen?

Answer 6

-occurs as a response to excessive extracellular or intracellular stress

Question 7

Define apoptosis

Answer 7

A morphological and biochemical form of programmed cell death that plays an essential role during the individuals life

Question 8

What is the difference in the roles of apoptosis and senescence?

Answer 8

Apoptosis- helps to balance the cell number at a constant rate
Senescence- takes place due to the ageing process

Question 9

What is the difference in the significance of apoptosis and senescence?

Answer 9

Apoptosis - chromosome condensation is significant

Senescence- irreversible arrest of cells during cell proliferation

Question 10

What is the difference how apoptosis and senescence is caused?

Answer 10

Apoptosis- different physiological and pathological conditions
Senescence- oxidative stress, DNA damage and alternation of genetic expression

Question 11

What is the difference in the regulation of apoptosis and senescence?

Answer 11

Apoptosis- intracellular proteolytic mechanisms

Senescence- genes involved in ageing mechanisms

Question 12

What is senescence caused by?

Answer 12

Telomere shortening
DNA damage
Oncogene activation
Oxidative stress

Question 13

What does SASP stand for?

Answer 13

Senescence-associated secretory pathways

Question 14

What does the SASP also secrete?

Answer 14

Inflammatory cytokines, Growth factors and proteases

Question 15

What did Leonard hayflick and Paul Moorhead discover in 1961?

Answer 15

Normal human fibroblasts in culture lasted only 50 cell population doubling before becoming senescent

Question 16

What is the hayflick limit?

Answer 16

Th number of times that a normal human cell population will divide before it becomes senescent

Question 17

What are the only immortal cultured cells?

Answer 17

Cancer cells- they never reach their hayflick limit

Question 18

What is cell lifespan?

Answer 18

The total number of doubling a cell population goes through before senescence, or the length of time for which a cell exists

Question 19

What are the morphological changes that take place in a senescent cell?

Answer 19

• larger and flatter cells
• prominent nuclei
• nuclear lamina degradation
• increase in vacuoles (vacuolised)
• chromatin reorganisation

Question 20

What are the biochemical and molecular changes a senescent cell goes through?

Answer 20

• beta-galactosidases and protein p16

- complex secretome involving inflammatory and proliferation products as well as changes in the extracellular matrix

Question 21

Do all senescent cells have all the biochemical markers?

Answer 21

No

Question 22

What is a telomere?

Answer 22

Regions at the end of chromosomes which are composed of TTAGGG.
DNA sequences whose function it is to preserve chromosomal integrity during each DNA replication thus preventing DNA damage

Question 23

What does the loss or breakage of a telomere result in?

Answer 23

Unstable chromosome ends which can be involved in recombination events or be degraded. Also the telomere flanking genes could be damaged

Question 24

What is telomeric DNA associated with?

Answer 24

A six member shelterin complex that facilitated the formation of loops which cap the chromosome end

Question 25

Why does progressive telomere shortening occur in all dividing cells?

Answer 25

Due to an incomplete lagging strand through DNA synthesis

Question 26

What is telomerase

Answer 26

Ribonuclearprotein enzyme which replicates telomeric DNA

Question 27

How does telomerase work?

Answer 27

Reverse transcribing DNA hexanes from RNA using its RNA subunit (TERC) and its protein component (TERT)

Question 28

What does TERC stand for?

Answer 28

Telomerase DNA component

Question 29

What does TERT stand for

Answer 29

Telomerase reverse transcriptase

Question 30

What are the two steps involved in telomerase elongating telomeric DNA?

Answer 30

Synthesis and translocation

Question 31

Give the steps involved in telomerase elongating telomeric DNA

Answer 31

• in the lagging strand, telomerase can bind the first few nucleotides of the template to the last telomere sequence of the chromosome
• it adds a new telomere repeat which is complementary to the sequence
• then it realigns with the new 3’ end of the telomere and repeats the process

Question 32

Where is telomerase activity happening in adult somatic cells (and how)?

Answer 32

Blood, skin, intestine

They don’t express TERT

Question 33

When is replicative senscence triggered in normal cells?

Answer 33

When the telomeres get quite short (1-5) telomeres

Question 34

What are germline cells?

Answer 34

Egg, Sperm and their diploid progenitors

Question 35

How do germline cells maintain all length telomeres?

Answer 35

They express TERT so are immortal

Question 36

How do cancer cells do uncontrolled division?

Answer 36

They activate telomerase

Question 37

What operates as a tumour suppressor pathway and what provides an escape that allows outgrowth of cells

Answer 37

Telomere shortening is a tumour suppressor pathway, but activation of telomerase provides an escape and allows an outgrowth with a rearranged genome

Question 38

What are some of the most common abnormalities found in cancer cells?

Answer 38

Expression of TERT
p53 defects
P16 defects

Question 39

What does the length of telomeres say about the health and age of a person?

Answer 39

The longer they are the healthier a person is

Question 40

What are expressed more in ageing tissues?

Answer 40

P16 and other senescence-associating proteins

Question 41

What varies at birth and how is this linked to age at death

Answer 41

Telomere length, the shorter at birth, the earlier you are likely to die

Question 42

Give some syndromes which are affected by telomerase length

Answer 42

Human senile defects, CVD, frailty, type 2 diabetes, neurodegeneration, cancer

Question 43

What do embryonic stem cells express to make them immortal?

Answer 43

TERT and telomerase

Question 44

How is bone marrow related to cell senescence

Answer 44

Older people show decreased immunity, increased bone marrow failure, decreased success rate at bone marrow donors. They have a reduced ability to proliferate marrow stem cells

Question 45

How is hair greying linked to cell senescence

Answer 45

Linked to decreased melanocyte stem cell maintenance in hair follicles (in mice)