Wk2 Cell Senescence Flashcards

0
Q

What are the features of senescence

A
Permanent growth arrest
Resistant apoptosis
Altered pattern if gene expression
Remain metabolically active
Inability of one cell to progress though the cell cycle
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1
Q

What is cell senescence

A

Process whereby cell stops dividing despite favorable conditions

It results in aging of cells and organisms and serves a tumour suppressor function

Senescent cells are found at sites of age related pathology such as osteoarthritis, atherosclerosis, and chronic heart failure

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2
Q

What causes cell senescence

A
Oncogene activation
Cytotoxic drugs
Cell culture
Oxidative stress
DNA damage
(NB) telomere dysfunction
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3
Q

Telomere dysfunction?

A

As the telomeres shorten eventually there will be important information lost

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4
Q

How do tumor cells overcome the telomere problem

A

telomerase

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5
Q

About telomerase

A

Enzyme that synthesize the G-rich strand of telomeres DNA

Somatic cells lack it (hatred ), this is possibly why we age

Cancer cells have active telomerases

Cancer formation requires the activation of telomerase to meet its requirements

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6
Q

What are the intrinsic inductors of cell senescence

A
stress*
Oncogenes*
Mitochondrial DNA damage*
Nucleoplasm dysfunction
Epigenetics
Auto phage
Micro-RNA
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7
Q

Extrinsic indicators of cell senescence?

A

Alteration in stem cell niches with aging:
Stem cell niches define the cells renewal capabilities and governs the factors influencing its survival

Alteration leads to an impairment of the stem cells characteristics and functions

  • spatial location
  • anchorage of stem cells to supporting cells
  • ECM (extra cellular matrix) stimulation and inhibitory signals
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8
Q

How does a cell become immortal

A

They overcome cell senescence
Senescence is stimulated by cut our suppressing functions of RB and p53, these functions are abrogated in immortalized cells

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9
Q

Name some random facts relating to immortalisation?

A

Immortal cells know how to stab alive their telomere ends. (Via telomerase upregulation )

Stem cells and germ cells maintain telomerase expression (but they keep in balance and this is a fine line)

Immortalisation is a prerequisite for further neoplasticism transformation

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10
Q

What is the antagonistic pleiotrophy hypothesis

A

Cellular processes that benefit young organisms may have unwanted effects in older organisms

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11
Q

What is aging

A

Reduction in the ability to preform homeostasis, maintain tissue or repair tissue following injury

The pool of stem cells in every tissue ages

Several environmental behavioral and genetic factors play a role in aging

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12
Q

Two defining characteristics of cancer (with reference to senescence)

A

They are immortal

They grow uncontrollably

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13
Q

Ways that stress induce cell senescence

A

genomic DNA damage

  • free radicals
  • UV light
  • ionizing radiation
  • Chemical substances

Double stranded breaks are the most deleterious form of DNA damage and may result in loss of genetic material

DNA repair is complicated, damage must be detected and repaired In the context of highly condensed chromatin fibers

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14
Q

Ways oncogenes induce cell senescence

A

Over expression of oncogenes
RAS-RAF-MEK signaling pathway
Over expression of oncogenes: EGGR, RAC1, RAF, MAPK, MEK
inactivation of tumour suppression genes: PTEN, p53, RB

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15
Q

Ways in which Mitochondrial DNA damage can induce senescence

A

Mitochondria are crucial in the development of aging and it generates the majority of energy the cell uses via the respiratory chain

Mitochondria produce ROS

Increased oxidative damage to mitochondrial DNA, proteins and lipids and the accumulation of point mutations

Decrease in mitochondrial metabolism