Cell Determination And Cell Senescence Flashcards
Define cell determination
When the cell fate becomes stable. It’s followed by differentiation. When a cell chooses a particular fate, it is said to be determined
Give the differences between cell determination and cell differentiation
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
Why does asymmetrical cell division happen?
The uneven distribution of cytoplasmic molecules (proteins or mRNAs) within a cell before it divides
What causes cell determination?
- inductive signals from neighbouring cells
- one group of cells influences the development of another group of cells
- pioneer factors
Define cellular senescence
Irreversible process in all cells arrest mechanism in which cells cease to divide
Why does cellular senescence happen?
-occurs as a response to excessive extracellular or intracellular stress
Define apoptosis
A morphological and biochemical form of programmed cell death that plays an essential role during the individuals life
What is the difference in the roles of apoptosis and senescence?
Apoptosis- helps to balance the cell number at a constant rate
Senescence- takes place due to the ageing process
What is the difference in the significance of apoptosis and senescence?
Apoptosis - chromosome condensation is significant
Senescence- irreversible arrest of cells during cell proliferation
What is the difference how apoptosis and senescence is caused?
Apoptosis- different physiological and pathological conditions
Senescence- oxidative stress, DNA damage and alternation of genetic expression
What is the difference in the regulation of apoptosis and senescence?
Apoptosis- intracellular proteolytic mechanisms
Senescence- genes involved in ageing mechanisms
What is senescence caused by?
Telomere shortening
DNA damage
Oncogene activation
Oxidative stress
What does SASP stand for?
Senescence-associated secretory pathways
What does the SASP also secrete?
Inflammatory cytokines, Growth factors and proteases
What did Leonard hayflick and Paul Moorhead discover in 1961?
Normal human fibroblasts in culture lasted only 50 cell population doubling before becoming senescent
What is the hayflick limit?
Th number of times that a normal human cell population will divide before it becomes senescent
What are the only immortal cultured cells?
Cancer cells- they never reach their hayflick limit
What is cell lifespan?
The total number of doubling a cell population goes through before senescence, or the length of time for which a cell exists
What are the morphological changes that take place in a senescent cell?
- larger and flatter cells
- prominent nuclei
- nuclear lamina degradation
- increase in vacuoles (vacuolised)
- chromatin reorganisation
What are the biochemical and molecular changes a senescent cell goes through?
- beta-galactosidases and protein p16
- complex secretome involving inflammatory and proliferation products as well as changes in the extracellular matrix
Do all senescent cells have all the biochemical markers?
No
What is a telomere?
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
What does the loss or breakage of a telomere result in?
Unstable chromosome ends which can be involved in recombination events or be degraded. Also the telomere flanking genes could be damaged
What is telomeric DNA associated with?
A six member shelterin complex that facilitated the formation of loops which cap the chromosome end
Why does progressive telomere shortening occur in all dividing cells?
Due to an incomplete lagging strand through DNA synthesis
What is telomerase
Ribonuclearprotein enzyme which replicates telomeric DNA
How does telomerase work?
Reverse transcribing DNA hexanes from RNA using its RNA subunit (TERC) and its protein component (TERT)
What does TERC stand for?
Telomerase DNA component
What does TERT stand for
Telomerase reverse transcriptase
What are the two steps involved in telomerase elongating telomeric DNA?
Synthesis and translocation
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
Where is telomerase activity happening in adult somatic cells (and how)?
Blood, skin, intestine
They don’t express TERT
When is replicative senscence triggered in normal cells?
When the telomeres get quite short (1-5) telomeres
What are germline cells?
Egg, Sperm and their diploid progenitors
How do germline cells maintain all length telomeres?
They express TERT so are immortal
How do cancer cells do uncontrolled division?
They activate telomerase
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
What are some of the most common abnormalities found in cancer cells?
Expression of TERT
p53 defects
P16 defects
What does the length of telomeres say about the health and age of a person?
The longer they are the healthier a person is
What are expressed more in ageing tissues?
P16 and other senescence-associating proteins
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
Give some syndromes which are affected by telomerase length
Human senile defects, CVD, frailty, type 2 diabetes, neurodegeneration, cancer
What do embryonic stem cells express to make them immortal?
TERT and telomerase
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
How is hair greying linked to cell senescence
Linked to decreased melanocyte stem cell maintenance in hair follicles (in mice)
