Ex2 L5 - Cellular Senescence Flashcards
(28 cards)
Sometimes “senescence” (not cellular senescence) is used as a synonym for…
aging
What happens in the S phase of the cell cycle?
duplicating of everything in the cell
The cell cycle forms…
2 identical daughter cells
What happens in interphase vs. mitosis?
interphase: preparing to divide
mitosis: dividing
Where are the cell cycle checkpoints and what are they checking for?
G1 - damaged DNA
S - unreplicated or damaged DNA
G2 - unreplicated or damaged DNA
Mitosis - chromosome misalignment
What is cellular senescence?
process where cells undergo permanent cell cycle arrest in response to certain stressors
What is the difference between senescence and quiescence?
senescence: permanent Go, possible to escape with more mutations
quiescence: temporary Go, can “easily” re-enter the cycle
Cellular senescence is a protective mechanism that…
allows cells to respond to potentially tumorigenic events, including:
- DNA damage
- activation/expression of oncogenes
- increased signals for growth (mitogens)
- oxidative stress
Senescent cells have a distinct ——- which includes 3 criteria:
phenotype:
- irreversible cell cycle arrest
- resist apoptosis
- altered cell function (metabolically active, but changes in function)
Senescent cells often have altered functions such as:
- chromatin rearrangement
- altered secretory function
-activation of tumor-suppressor genes
Describe senescence initiation
Senescence inducing signals like oncogene activation or DNA damage trigger the cell to exit the cell cycle permanently
Describe early senescence
- chromatin remodeling
- pancaked cells (flat, enlarged morphology)
- non uniform membrane
- loss of Lamin B1 (parallel to progeroid syndromes)
- more extensive Golgi (more secretion)
Describe late senescence
- triggered by aging or long-term damage
- after time, there is chronic inflammation (inflammaging) and diversification of the senescent phenotype
Before Hayflick, it was believed that cells…
were immortal
- Alexis Carrel (1912)
- said the limited capacity for cell division was thought to be an artifact of improper tissue culture technique
What is the Hayflick limit?
Leonard Hayflick, demonstrated a limited capacity for cell division
- found that after about 50 divisions cells enter a resting phase
The current belief about cell mortality is that…
- most cells undergo a finite number of divisions
- telomeres shorten with each division
- most cells undergo apoptosis or senescence when they reach the limit
- stem cells don’t have this limit, and cancer cells override it
What are the genes involved in senescence? What do they do?
- tumor suppressor genes promote senescence
- ex: p53 (detect DNA damage)
- ex: pRb (retinoblastoma protein, G1 checkpoint protein)
- induce cell cycle arrest in response to potentially tumorigenic events
What happened to mice without tumor suppressor genes?
they have high incidence of cancer at a younger age
Mutation of tumor suppressor genes –>
cancer
Cells from older individuals divide…
less frequently
Cells from individuals with progeroid syndromes divide…
less frequently
Senescent cells accumulate over time and cause…
age related pathologies
A hallmark trait of a senescent phenotype is:
altered cell function
- senescence-associated secretory phenotype (SASP)
What are SASPs? What do they cause?
senescence-associated secretory phenotype
- senescent cells secrete growth factors, inflammatory cytokines, ECM degrading enzymes, etc.
- pro-inflammatory: good for wound healing but bad for tossie and organ function
- ultimately contributes to aging and age-related pathologies
