Cell Senescence Flashcards
What is the single biggest risk factor developing cancer?
Age.
What is cell senescence?
A mechanism for preventing the proliferation of potential cancer cells.
Which stages of the cell cycle are most likely times senescent cells to stop proliferating?
G1 phase
G2 phase
What could cause a proliferating cell to become senescent?
Excess cell division
Short telomeres
Activated oncogene
Cell stress or damage
What is a nevus?
A mole
When are nevi acquired?
In utero or soon after birth.
How are nevi formed?
A melanocyte which acquires an activated BRAF or NRAS oncogene, the cells can proliferate and expand to form a cluster of pigmented melanocytes.
Why do nevi not progress to melanoma more frequently?
The cells are kept in a proliferation arrested state called cellular senescence.
Why do melanocytes sometimes progress to melanoma?
Partially due to inactivation of p16 or PTEN.
How was senescence originally discovered?
Hayfleck was growing cells in culture and found eventually cells just stop growing.
- the Hayfleck limit
Give examples of markers of senescence.
β- galactasidose, p16
What do senescent cells secrete?
Various cytokines and chemokines such as VEGF, IL6, IL8, Matrix metalloproteases.
Why is the senescence associated secretory phenotype thought to be important?
By bringing in immune cells it might promote clearance of damaged cells.
By secreting inflammatory molecules it could be detrimental to a tissue in the long term.
How do senescent cells promote tissue aging?
Blocking cell renewal.
Driving chronic inflammation.
They are inherently damaged cells that have a tendency to become diseased.
How do senescent cells inhibit cancer?
Damaged cells are prevented by progressing to cancer by senescence.
How do senescent cells promote cancer?
Over years and decades as senescent cells accumulate in tissues, long term effects such as chronic inflammation can promote cancer.
What are telomeres?
The ends of chromosomes.
What happens to telomeres every time a cell divides?
They get a bit shorter.
Why do telomeres shorten?
A gap is left where the RNA primer was.
Which kinases does DNA damage activate?
ATR/ATM kinases. They then activate Chk1/Chk2 kinases, which activate p53.
What does p53 activate?
p21, which stops cell proliferation.
What effect does p16 have on proliferation?
It inhibits proliferation.
What is the mechanism by which p16 is activated in senescent cells?
In proliferating cells p16 protein is repressed by polycomb and noncoding RNA and other proteins.
In senescent cells p16 gets activated because these various processes are reversed.
Are there more p16 positive cells in younger adults or older adults?
More p16 positive cells in older adults.
Which 2 SNPs were found to be related to ageing?
One in major histocompatibility complex
Another at locus that encodes a lot of tumour suppressors.