Cell Determination And Cell Senescence Flashcards

1
Q

Define cell determination

A

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

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2
Q

Give the differences between cell determination and cell differentiation

A

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

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3
Q

Why does asymmetrical cell division happen?

A

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

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4
Q

What causes cell determination?

A
  • inductive signals from neighbouring cells
  • one group of cells influences the development of another group of cells
  • pioneer factors
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5
Q

Define cellular senescence

A

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

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6
Q

Why does cellular senescence happen?

A

-occurs as a response to excessive extracellular or intracellular stress

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7
Q

Define apoptosis

A

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

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8
Q

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

A

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

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9
Q

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

A

Apoptosis - chromosome condensation is significant

Senescence- irreversible arrest of cells during cell proliferation

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10
Q

What is the difference how apoptosis and senescence is caused?

A

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

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11
Q

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

A

Apoptosis- intracellular proteolytic mechanisms

Senescence- genes involved in ageing mechanisms

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12
Q

What is senescence caused by?

A

Telomere shortening
DNA damage
Oncogene activation
Oxidative stress

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13
Q

What does SASP stand for?

A

Senescence-associated secretory pathways

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14
Q

What does the SASP also secrete?

A

Inflammatory cytokines, Growth factors and proteases

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15
Q

What did Leonard hayflick and Paul Moorhead discover in 1961?

A

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

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16
Q

What is the hayflick limit?

A

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

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17
Q

What are the only immortal cultured cells?

A

Cancer cells- they never reach their hayflick limit

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18
Q

What is cell lifespan?

A

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

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19
Q

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

A
  • larger and flatter cells
  • prominent nuclei
  • nuclear lamina degradation
  • increase in vacuoles (vacuolised)
  • chromatin reorganisation
20
Q

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

A
  • beta-galactosidases and protein p16

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

21
Q

Do all senescent cells have all the biochemical markers?

22
Q

What is a telomere?

A

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

23
Q

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

A

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

24
Q

What is telomeric DNA associated with?

A

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

25
Why does progressive telomere shortening occur in all dividing cells?
Due to an incomplete lagging strand through DNA synthesis
26
What is telomerase
Ribonuclearprotein enzyme which replicates telomeric DNA
27
How does telomerase work?
Reverse transcribing DNA hexanes from RNA using its RNA subunit (TERC) and its protein component (TERT)
28
What does TERC stand for?
Telomerase DNA component
29
What does TERT stand for
Telomerase reverse transcriptase
30
What are the two steps involved in telomerase elongating telomeric DNA?
Synthesis and translocation
31
Give the steps involved in telomerase elongating telomeric DNA
- 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
32
Where is telomerase activity happening in adult somatic cells (and how)?
Blood, skin, intestine | They don’t express TERT
33
When is replicative senscence triggered in normal cells?
When the telomeres get quite short (1-5) telomeres
34
What are germline cells?
Egg, Sperm and their diploid progenitors
35
How do germline cells maintain all length telomeres?
They express TERT so are immortal
36
How do cancer cells do uncontrolled division?
They activate telomerase
37
What operates as a tumour suppressor pathway and what provides an escape that allows outgrowth of cells
Telomere shortening is a tumour suppressor pathway, but activation of telomerase provides an escape and allows an outgrowth with a rearranged genome
38
What are some of the most common abnormalities found in cancer cells?
Expression of TERT p53 defects P16 defects
39
What does the length of telomeres say about the health and age of a person?
The longer they are the healthier a person is
40
What are expressed more in ageing tissues?
P16 and other senescence-associating proteins
41
What varies at birth and how is this linked to age at death
Telomere length, the shorter at birth, the earlier you are likely to die
42
Give some syndromes which are affected by telomerase length
Human senile defects, CVD, frailty, type 2 diabetes, neurodegeneration, cancer
43
What do embryonic stem cells express to make them immortal?
TERT and telomerase
44
How is bone marrow related to cell senescence
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
45
How is hair greying linked to cell senescence
Linked to decreased melanocyte stem cell maintenance in hair follicles (in mice)