Determination and Cellular Senescence Flashcards
What is cell determination?
Cell determination- a process whereby cell fate becomes stable
It is followed by cell differentiation.
When a cell chooses a particular “fate”, it is said to be determined
Implies a stable change
occurs in totipotent, embryonic stem cells
As a result of asymmetric segregation of cytoplasmic determinants
What is asymmetric segregation and how does it occur?
Asymmetrical cell division due to differential distribution of cytoplasmic molecules (proteins or mRNAs) within a cell before it divides
Two daughter cells= different dates- different gene expression profile
Inductive signals from neighbouring cells is the most common cause of cell determination
One group of cells influences the development of another group of cells
What are p-granules?
P-granules are a class of perinuclear granules specific to the germline
What is the role of pioneer factors in cell determination?
Pioneer factors/master regulators together with co-factors are key in cell-fate decision making
What is cell senescence?
Cell senescence: irreversible cell-cycle arrest mechanism in which cells cease to divide
Occurs as a response to excessive extracellular or intracellular stress
Cell senescence has the potential to influence neighbouring cells through secreted soluble factors
Strongly implicated in symptoms of ageing but also an important defence against cancer
What is the difference between cell senescence and apoptosis?
Cell senescence: irreversible cell-cycle arrest mechanism in which cells cease to divide
Role is that it takes place during the process of ageing
Apoptosis: is a morphologically and biochemically form of programmed cell death that plays an essential role during the individual’s life
Role- helps to balance the cell number at a constant rate
What is cell lifespan?
Cell lifespan is the total number of doublings that a cell population goes through before senescence
The length of time for which a cell exists
Normal cells have a finite lifespan as opposed to immortal cells (e.g. cancer cells), which can divide forever
What is the Hayflick Limit?
The Hayflick Limit is the number of times that a normal human cell population will divide before cell division stops
What morphological and biochemical changes does cell senescence imply?
A. Morphological changes:
Larger and flat cells
Prominent nucleoli
Nuclear lamina degradation
Vacuolised (vacuoles increase in number)
Chromatin reorganisation
B. Biochemical and molecular changes
Two of the best known molecular markers are lysosomal b-galactosidase and protein p16
Complex secretome involving inflammatory and proliferation products as well as changes in extracellular matrix
SASP: Senescence Associated Secretory Phenotype consists of inflammatory cytokines, growth factors and proteases.
What are the main mechanisms associated with controlling cellular senescence?
P53 and retinoblastoma pathways are the main mechanisms associated with controlling cellular senescence
Telomere attrition is one of the trying factors of cell senescence
What are telomeres?
Telomeres: regions at the end of the chromosomes composed of TTAGGGn DNA sequences whose function is to preserve chromosome integrity during each DNA replication thus preventing from DNA damage (part of constitutive heterochromatin)
What can loss of telomeres result in?
Loss of telomere by chromosome breakage results in unstable chromosome end that can fuse with other broken chromosomes or be involved in recombination event or be degraded
It can also involve the damage of telomere-flanking genes- if telomere shorten too much the genes flaking telomeres are damaged too
How are telomeres structured?
Telomeric DNA is associated with a six-member protein shelterin complex that facilitates the formation of loops which ‘cap/shield’ the chromosome end
How does telomere shortening happen and how is the problem dealt with?
Progressive telomere shortening occurs in all dividing normal cells mainly due to incomplete lagging-strand DNA synthesis/replication of that area
Telomerase: ribonucleoprotein enzyme which replicates telomeric DNA by reverse transcribing DNA hexamers (TTAGGG) from RNA using its RNA subunit (TERC- telomeric RNA component) and its protein component (TERT- telomerase reverse transcriptase)
Telomerase elongates telomeric DNA by repetition of two-steps cycle: synthesis and translocation
How do telomere length and telomerase activity vary across cells?
Telomere length is highly variable and telomerase activity normally absent from adult somatic cells except for highly-proliferative tissues such as blood, skin and intestine (they do not express TERT)
Replicative senescence is triggered in normal cells when telomere(s) get quite short (about 1-5 telomeres sufficient)
