WEEK 2: cell ageing and cell death Flashcards
what are the two biological theories of ageing?
- the programmed theory: ageing has an internal clock
- error theory (damage) : ageing is a result of internal/external assaults that damage cells and organs
what is cellular senescence (pillar of ageing)
the irreversible block in proliferation (the process in which cells cease to divide)
‘zombie cells’
What is the importance of cellular senescence?
- it ensures the cell corrects DNA mutations by stopping it from dividing
-hence prevents the accumulation of cells with damaged DNA that can be cancerous
What are the benefits of senescent cells?
- used in wound healing and tissue regeneration by expressing cytokines that aid in tissue remodelling
-when cells become infected, senescence stops the division of the cell and the virus cannot survive
-they activate the innate immune system and aid in clearance of infected cells - they are essential for tumor suppression
why are senescent cells harmful later in life?
- the accumulation of senescent cells can stimulate angiogenesis - the formation of new blood vessels
-it can stimulate tumour growth by the secretion of senescence associated inflammatory factors
-ends up causing tissue degeneration and lead to various diseases due to senescence of immune cells
what is the second pillar of ageing
telomere shortening
what are telomeres?
protective caps at the end of chromosomes that serve to protect genetic material from degradation and prevent chromosomes from sticking to each other -
what role to telomeres play in cell ageing?
each time a cell divides, telomeres shorten - this limits cell division as the cell can no longer divide properly
how do telomeres protect the end of chromosomes?
they form a protective structure together with the protein complex shelterin
What is the name of the enzyme that ensures repetitive DNA sequences of the end of chromosomes are maintained?
telomerase
Where is telomerase not present and what effect does this have?
It is not present in adult somatic cells, hence as with each cell division, the telomeres start to decrease in length
What is the 3rd hallmark of ageing?
DNA damage
What is DNA damage caused by?
External insults: UV, chemicals, pollutants
Internal insults: metabolic bi-products, ROS
DNA replicatin/proliferation: rapid prolif. promoting DNA damage causing senescence
Why can DNA repair enzymes sometimes fail at repairing mutations?
If the error rate is too high, some mutations are not corrected and copied into daughter cells
What does the DNA damage theory state?
biological ageing is a result of accumulated DNA damage that is unrepaired and can alter the function/become detrimental to a cell
What 3 choices does a cell have once in undergoes extensive damage?
apoptosis, alter the function of the cell so that the cell cannot function properly, or undergo senescence
what diseases have allowed us to learn more about the mechanisms of aging?
- progeroid syndrome- when individuals age prematurely- the integrity of DNA is compromised, affecting multitudinous features in the cell leading to premature aging
- Hutchinson Gilford Progeria Syndrome
What is DNA wrapped around inside out cells?
proteins called histones
What is it called when 146 base pairs of DNA wrap around these histones?
Nucleosome
How is DNA affected in low density nucleosome structures?
DNA is more exposed and prone to becoming damaged
How is DNA affected in high density nucleosome strcutures
DNA is more protected
What does DNA methylation do?
it is epigenetic modification that leads to chromatin compation and protection of the DNA.
What is epigenetics?
heritable changes in gene expression that do not involve changes to the DNA sequence itself- instead it’s dependent on DNA modifications/histone modifications
What is epigenetic drift?
As cells age, they undergo epigenetic drift, this is the divergence of the epigenome due to age.
There is a decrease in DNA methylation which leads to open chromatin, leading to genetic instability because DNA is more prone to becoming damaged. this leads to cellular senescence, apoptosis, cellular dysfunction, and is caused by lots of factors, including diet, stress, chemical exposure, etc.