Wk2 Cell Senescence Flashcards
What are the features of senescence
Permanent growth arrest Resistant apoptosis Altered pattern if gene expression Remain metabolically active Inability of one cell to progress though the cell cycle
What is cell senescence
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
What causes cell senescence
Oncogene activation Cytotoxic drugs Cell culture Oxidative stress DNA damage (NB) telomere dysfunction
Telomere dysfunction?
As the telomeres shorten eventually there will be important information lost
How do tumor cells overcome the telomere problem
telomerase
About telomerase
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
What are the intrinsic inductors of cell senescence
stress* Oncogenes* Mitochondrial DNA damage* Nucleoplasm dysfunction Epigenetics Auto phage Micro-RNA
Extrinsic indicators of cell senescence?
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
How does a cell become immortal
They overcome cell senescence
Senescence is stimulated by cut our suppressing functions of RB and p53, these functions are abrogated in immortalized cells
Name some random facts relating to immortalisation?
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
What is the antagonistic pleiotrophy hypothesis
Cellular processes that benefit young organisms may have unwanted effects in older organisms
What is aging
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
Two defining characteristics of cancer (with reference to senescence)
They are immortal
They grow uncontrollably
Ways that stress induce cell senescence
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
Ways oncogenes induce cell senescence
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