Cellular Death And Neurodegeneration Flashcards
Cellular senescence
Proteins and DNA accumulate damage
Changes in gene transcription
Senescence
Deterioration of cellular function and the overall organism over time
Organismal senescence
Summation of loss of cellular function
Increased chance of age associated disease
2 types of aging
- Chronological
2. Biological
Chronological aging
Measured by the passing of time
Biological aging
Difficult to measure
“Dog years”
How long you have had a car (chronological) v. How many miles it has (biological)
Do all cells/organisms age?
Cancer cells never stop dividing–immortal
Hydra–regenerates from any portion of its body; cells are constantly dividing, removing old or damaged cells
Budding yeast–mother cell accumulates bud scars/damaged DN and proteins as they divide
Sources of cellular damage
- Environment
- Metabolism
- Infection
Environment
Cells are damaged by chemical compounds that are ingested/inhaled
Destructive forms of radiation
Pollutants–air, water
UV radiation
Reactive Oxygen Species
Extremely chemically reactive oxygen molecules
Oxygen molecule–unaired electrons; toxic to cell
Only 7 electrons in valence shell–will be highly reactive and make bonds/destroy existing bonds of other molecules in order to satisfy octet rule
Made in mitochondria
ROS damage proteins, DNA, lipids, etc
Cells deal with them using enzymes and antioxidants (proteins that can act as sensors)
Elevated in all major neurodegenerative diseases
How do cells deal with damaged proteins and organelles?
Autophagy (“self-eating”)
Autophagy
“Self-eating”
Digestion of unnecessary or disfunctional cellular components (misfolded proteins to full organelles)
When regulated, normal breakdown or material into its component parts
3 steps
Recycle
Protein-> amino acids
Misfolded proteins and amyloid fibers can be broken down through autophagy
Senescent cells have significantly reduced levels of autophagy–aggregates and lysosomes with material inside are not broken down; toxic to cell
3 steps of autophagy
- Isolate material in membrane bound vesicle
- Fuse with the lysosome
- Break down isolated material
Programmed cellular death
Any self regulated induction of cellular death
Cell decides its own fate and induces its own destruction
Atrophic factors
Planned; does not only occur when something goes wrong
Atrophic factors
Factors that force a cell to induce programmed cellular death
- decreased workload
- diminished blood supply
- inadequate nutrition
- loss of growth stimulation
- stimulated tissue morphologies
Programmed cellular death pathways
Apoptosis--"self-destruction" Cell's response to something bad (stress) Heat Radiation Lack of nutrients/oxygen
Neurodegeneration
Loss of neuronal structure and function
Post-mitotic–can’t remove cell damage through cell division
Size–long axons that are sensitive to damage
Neurodegeneration in the brain
Central nervous system
Oligodendrocytes:
- die if not connected to active neurons
- do not clean extracellular space around healthy cells
Neurodegeneration in the brain
Periphery nervous system
Schwann cells:
- aid in neuronal regrowth
- clear away myelin debris
- survive on their own
Lifespan extension
Reduce oxidative damage–calorie restriction,”anti-aging” compounds in red wine (resveratrol)
Need autophagy
