Ex2 L5 - Cellular Senescence Flashcards

1
Q

Sometimes “senescence” (not cellular senescence) is used as a synonym for…

A

aging

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2
Q

What happens in the S phase of the cell cycle?

A

duplicating of everything in the cell

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3
Q

The cell cycle forms…

A

2 identical daughter cells

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4
Q

What happens in interphase vs. mitosis?

A

interphase: preparing to divide
mitosis: dividing

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5
Q

Where are the cell cycle checkpoints and what are they checking for?

A

G1 - damaged DNA
S - unreplicated or damaged DNA
G2 - unreplicated or damaged DNA
Mitosis - chromosome misalignment

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6
Q

What is cellular senescence?

A

process where cells undergo permanent cell cycle arrest in response to certain stressors

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7
Q

What is the difference between senescence and quiescence?

A

senescence: permanent Go, possible to escape with more mutations

quiescence: temporary Go, can “easily” re-enter the cycle

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8
Q

Cellular senescence is a protective mechanism that…

A

allows cells to respond to potentially tumorigenic events, including:
- DNA damage
- activation/expression of oncogenes
- increased signals for growth (mitogens)
- oxidative stress

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9
Q

Senescent cells have a distinct ——- which includes 3 criteria:

A

phenotype:
- irreversible cell cycle arrest
- resist apoptosis
- altered cell function (metabolically active, but changes in function)

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10
Q

Senescent cells often have altered functions such as:

A
  • chromatin rearrangement
  • altered secretory function
    -activation of tumor-suppressor genes
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11
Q

Describe senescence initiation

A

Senescence inducing signals like oncogene activation or DNA damage trigger the cell to exit the cell cycle permanently

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12
Q

Describe early senescence

A
  • chromatin remodeling
  • pancaked cells (flat, enlarged morphology)
  • non uniform membrane
  • loss of Lamin B1 (parallel to progeroid syndromes)
  • more extensive Golgi (more secretion)
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13
Q

Describe late senescence

A
  • triggered by aging or long-term damage
  • after time, there is chronic inflammation (inflammaging) and diversification of the senescent phenotype
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14
Q

Before Hayflick, it was believed that cells…

A

were immortal
- Alexis Carrel (1912)
- said the limited capacity for cell division was thought to be an artifact of improper tissue culture technique

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15
Q

What is the Hayflick limit?

A

Leonard Hayflick, demonstrated a limited capacity for cell division
- found that after about 50 divisions cells enter a resting phase

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16
Q

The current belief about cell mortality is that…

A
  • 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
17
Q

What are the genes involved in senescence? What do they do?

A
  • 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
18
Q

What happened to mice without tumor suppressor genes?

A

they have high incidence of cancer at a younger age

19
Q

Mutation of tumor suppressor genes –>

A

cancer

20
Q

Cells from older individuals divide…

A

less frequently

21
Q

Cells from individuals with progeroid syndromes divide…

A

less frequently

22
Q

Senescent cells accumulate over time and cause…

A

age related pathologies

23
Q

A hallmark trait of a senescent phenotype is:

A

altered cell function
- senescence-associated secretory phenotype (SASP)

24
Q

What are SASPs? What do they cause?

A

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
25
Q

Regarding diabetes as an example, SASP causes release of growth factors/inflammatory cytokines and causes:

A

paracrine effects:
- tissue dysfunction
- diabetic complications

systemic effects:
- inflammation
- insulin resistance

both together worsen T2D

26
Q

Senescent cells accumulate, and if something goes wrong…

A

they can acquire protumorigenic tissue mechanisms that allow them to escape senescence and cause cancer

27
Q

To eliminate senolytic cells, we would want to create a drug that targeted…

A

the pathways that block apoptosis in senescent cells - this way it doesn’t affect healthy cells because they do not have the anti-apoptotic pathways

28
Q

What are the pros and cons of inhibiting senescence?

A

pros:
- reduce inflammation that leads to age-related diseases
- eliminate cells that have the potential to escape senescence and form tumors

cons:
- cells that should become senescent (because they have DNA damage, etc.) will remain active and continue dividing - could cause many issues or cancer
- eliminating senescent cells can impair wound healing